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101. Regulator of Calcineurin 1 (RCAN1)

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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102. RGS 12/Regulator of G-Protein Signaling 12 (AGS6)

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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103. Rpt, Regulatory particle triple-A (Rpt) Subunits of 26S Proteasomes

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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104. Rsk-Like (RSKL)

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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105. Rh-Related Antigen

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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106. RANK and RANKL

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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107. ROCK: ROK kinase

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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108. RING Finger Protein 85 (RNF85)

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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109. Ribosomal Protein S6 Kinase, Polypeptide 5

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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110. RGS Proteins

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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111. Rab7a in Endocytosis and Signaling

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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112. Reggie-2 (Reg-2)

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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113. R7 Binding Protein (R7BP)

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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114. Rho Guanine Nucleotide Exchange Factor 25

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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115. RhoC (RHOC)

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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116. Regulators of G-Protein Signaling

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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117. Ryanodine-Sensitive Ca2+ Release Channels

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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118. Ras Guanyl Nucleotide-Releasing Protein 1

Author

Kirill A. Martemyanov, Pooja Parameswaran, Irene Aligianis, Mark Handley, Marga Gual-Soler, Tomohiko Taguchi, Jennifer L. Stow, Carol Wicking, Soumik BasuRay, Jacob O. Agola, Patricia A. Jim, Matthew N. Seaman, Angela Wandinger-Ness, Heather H. Ward, Diamantis Konstantinidis, Theodosia A. Kalfa, Andrea Varga, Manuela Baccarini, Debbie L. Hay, Patrick M. Sexton, David R. Poyner, Carlo Petosa, Tomoki Nakashima, Hiroshi Takayanagi, Hoa B. Nguyen, Lawrence A. Quilliam, Michael S. Samuel, Philip E. Lapinski, Philip D. King, Eugenio Santos, Alberto Fernández-Medarde, John J. Priatel, Kevin Tsai, Kenneth W. Harder, Jose-Luis González de Aguilar, Pavel P. Philippov, Evgeni Yu Zernii, Masakazu Fujiwara, Mohammad Ghazizadeh, Roger J. Summers, Michelle L. Halls, Emma T. Westhuizen, Scott A. Busby, Thomas P. Burris, David P. Siderovski, Adam J. Kimple, Zhihui Xie, Kirk M. Druey, Nicolas Reymond, Francisco M. Vega, Anne J. Ridley, Gregory G. Tall, Weikang Cai, Jennifer L. Rudolph, Douglas A. Andres, John Colicelli, Pamela Y. Ting, Christine Janson, Michael F. Olson, James P. Brody, Julie A. Maupin-Furlow, Hugo V. Miranda, Philippe P. Roux, Filip Van Petegem, and Kelvin Lau

Published
2012
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119. Rho-GTPases in Embryonic Stem Cells

Author

Michael F. Olson and Michael S. Samuel

Subjects
RHOA, GTP', biology, Chemistry, biology.protein, RAC1, CDC42, GTPase, Actin cytoskeleton, Filopodia, Actin, Cell biology
Abstract

The Rho family of small GTP-binding proteins is comprised of 22 members, including the most well characterized members RhoA, Rac1 and Cdc42 (Jaffe and Hall 2005). The Rho family proteins share a high degree of homology with the Ras proto-oncogene, and indeed were first identified as a result of this similarity (Ras homologue). Activity of these proteins is dependent upon their nucleotide binding state; inactive when associated with GDP but active following exchange of GDP for GTP, which induces conformational changes that promote association/activation of downstream effector proteins. The GDP/GTP cycle is regulated by GAPs that accelerate GTP hydrolysis by providing a critical catalytic amino acid leading to a return to the inactive state (Bernards and Settleman 2005), and GEFs that promote guanine nucleotide exchange and consequent Rho activation (Rossman et al. 2005). The number of GAPs and GEFs far exceeds the number of Rho proteins, and the roles of individual GAPs and GEFs in specific cell types and biological processes is currently an intensively studied field. Although united by homology and function as regulators of the actin cytoskeleton, each of RhoA, Rac1 and Cdc42 has a distinct role in the organization of actin structures (Figure 1). RhoA is principally involved with the production of actin-myosin bundles and the generation of actomyosin contractile force. Rac1 contributes to the formation of actin meshworks that result in the emergence of large protrusive structures that lead to spreading or, if occurring in a polarized manner, will contribute to motility. Cdc42 promotes the formation of actin-rich filopodia. Together, coordinated programs of RhoA, Rac1 and Cdc42 activation/inactivation play prominent roles in processes such as endocytosis/exocytosis, adhesion and motility, which may subsequently impact upon proliferation and death/survival. Recent advances in the development of activation-state sensitive fluorescent probes have allowed temporal and spatial analysis of Rho protein activation, which has added significantly to our appreciation of Rho regulation and function (Hodgson et al. 2010). Much of the early research on Rho protein function relied upon over-expression of dominant-negative mutants that reduced affinity for GTP and constitutively-active mutants that reduced GTP hydrolysis; however, more refined analysis has become possible with the rise of RNAi and knockout methodologies (Heasman and Ridley 2008). The study of Rho family proteins has historically focused on their roles as molecular switches acting downstream of cell surface receptors to regulate the actin cytoskeleton (Jaffe and Hall 2005). Significant effort has gone into classifying signaling from Rho proteins into

Published
2011
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120. p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival

Author

Owen J. Sansom, Filipe C. Lourenço, June Munro, Karim Bensaad, Kevin M. Ryan, Jenifer Wood, Karen H. Vousden, Daniel R. Croft, Michael F. Olson, Michael S. Samuel, Diane Crighton, Croft, Daniel R, Crighton, Diane, Samuel, Michael S, Lourenco, Filipe C, Munro, June, Wood, Jenifer, Bensaad, Karim, Vousden, Karen H, Sansom, Owen J, Ryan, Kevin M, and Olson, Michael F

Subjects
rho GTP-Binding Proteins, p53, Chromatin Immunoprecipitation, Transcription, Genetic, Cell Survival, DNA damage, Immunoblotting, RhoC, Fluorescent Antibody Technique, Antineoplastic Agents, Apoptosis, cofilin, Biology, Cell fate determination, Lim kinase, Mice, LIMK, Cell Line, Tumor, Animals, Humans, RNA, Small Interfering, Cytoskeleton, Molecular Biology, Actin, rho-Associated Kinases, Lim Kinases, cytoskeleton, Cell Biology, Microarray Analysis, Actin cytoskeleton, Actins, Cell biology, Gene Expression Regulation, rhoC GTP-Binding Protein, Gene Knockdown Techniques, biology.protein, Cancer research, Original Article, Tumor Suppressor Protein p53, Signal transduction, actin, DNA Damage, Signal Transduction
Abstract

The central arbiter of cell fate in response to DNA damage is p53, which regulates the expression of genes involved in cell cycle arrest, survival and apoptosis. Although many responses initiated by DNA damage have been characterized, the role of actin cytoskeleton regulators is largely unknown. We now show that RhoC and LIM kinase 2 (LIMK2) are direct p53 target genes induced by genotoxic agents. Although RhoC and LIMK2 have well-established roles in actin cytoskeleton regulation, our results indicate that activation of LIMK2 also has a pro-survival function following DNA damage. LIMK inhibition by siRNA-mediated knockdown or selective pharmacological blockade sensitized cells to radio- or chemotherapy, such that treatments that were sub-lethal when administered singly resulted in cell death when combined with LIMK inhibition. Our findings suggest that combining LIMK inhibitors with genotoxic therapies could be more efficacious than single-agent administration, and highlight a novel connection between actin cytoskeleton regulators and DNA damage-induced cell survival mechanisms. Refereed/Peer-reviewed

Published
2011

121. Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo

Author

David Tosh, Helen E. Abud, Owen J. Sansom, Inke S. Näthke, Michael Buchert, Andrew G. Jarnicki, Maree C. Faux, Valerie Meniel, Catherine E Winbanks, Zoë D. Burke, Michael S. Samuel, Joan K. Heath, Ian P. Newton, Alan Richard Clarke, Steven A. Stacker, Hiromu Suzuki, Dimitris Athineos, Matthias Ernst, Joerg Huelsken, Buchert, Michael, Athineos, Dimitris, Abud, Helen E, Burke, Zoe D, Faux, Maree C, Samuel, Michael S, Jarnicki, Andrew G, Winbanks, Catherine E, Newton, Ian P, Meniel, Valerie S, Suzuki, Hiromu, Stacker, Steven A, Näthke, Inke, Tosh, David, Huelsken, Joerg, Clarke, Alan R, Heath, Joan K, Sansom, Owen J, and Ernst, Matthias

Subjects
Male, Cancer Research, Cellular differentiation, medicine.disease_cause, recombinant proteins, Cell Biology/Cell Signaling, Developmental Biology/Pattern Formation, Mice, 0302 clinical medicine, Intestinal mucosa, antigen-presenting cells, Intestinal Mucosa, Genetics and Genomics/Genetics of Disease, Cells, Cultured, beta Catenin, Genetics (clinical), Developmental Biology/Embryology, Mice, Knockout, 0303 health sciences, Wnt signaling pathway, LRP5, 3. Good health, Intestines, Liver, 030220 oncology & carcinogenesis, alleles, Head morphogenesis, Female, carcinogenesis, Research Article, Signal Transduction, Beta-catenin, lcsh:QH426-470, Adenomatous Polyposis Coli Protein, Oncology/Gastrointestinal Cancers, Gastroenterology and Hepatology, Biology, Wnt3 Protein, RC0254, 03 medical and health sciences, Genetics, medicine, Animals, Allele, Genetics and Genomics/Cancer Genetics, QH426, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Wnt signaling cascade, Fibroblasts, Embryo, Mammalian, Mice, Inbred C57BL, Wnt Proteins, lcsh:Genetics, developmental signaling, biology.protein, Cancer research, gastrointestinal tract, Carcinogenesis, embryos, Developmental Biology
Abstract

Contributions of null and hypomorphic alleles of Apc in mice produce both developmental and pathophysiological phenotypes. To ascribe the resulting genotype-to-phenotype relationship unambiguously to the Wnt/β-catenin pathway, we challenged the allele combinations by genetically restricting intracellular β-catenin expression in the corresponding compound mutant mice. Subsequent evaluation of the extent of resulting Tcf4-reporter activity in mouse embryo fibroblasts enabled genetic measurement of Wnt/β-catenin signaling in the form of an allelic series of mouse mutants. Different permissive Wnt signaling thresholds appear to be required for the embryonic development of head structures, adult intestinal polyposis, hepatocellular carcinomas, liver zonation, and the development of natural killer cells. Furthermore, we identify a homozygous Apc allele combination with Wnt/β-catenin signaling capacity similar to that in the germline of the Apcmin mice, where somatic Apc loss-of-heterozygosity triggers intestinal polyposis, to distinguish whether co-morbidities in Apcmin mice arise independently of intestinal tumorigenesis. Together, the present genotype–phenotype analysis suggests tissue-specific response levels for the Wnt/β-catenin pathway that regulate both physiological and pathophysiological conditions., Author Summary Germline or somatic mutations in genes are the underlying cause of many human diseases, most notably cancer. Interestingly though, even in situations where every cell of every tissue of an organism carries the same mutation (as is the case for germline mutations), some tissues are more susceptible to the development of disease over time than others. For example, in familial adenomatous polyposis (FAP), affected persons carry different germline mutations in the APC gene and are prone to developing cancers of the colon and the rectum—and, less frequently, cancers in other tissues such as stomach, liver, and bones. Here we utilize a panel of mutant mice with truncating or hypomorphic mutations in the Apc gene, resulting in different levels of activation of the Wnt/β-catenin pathway. Our results reveal that different pathophysiological outcomes depend on different permissive signaling thresholds in embryonic, intestinal, and liver tissues. Importantly, we demonstrate that reducing Wnt pathway activation by 50% is enough to prevent the manifestation of embryonic abnormalities and disease in the adult mouse. This raises the possibility of developing therapeutic strategies that modulate the activation levels of this pathway rather than trying to “repair” the mutation in the gene itself.

Published
2010
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122. The Rho-regulated ROCK kinases in cancer

Author

Michael F. Olson, Pamela A. Lochhead, Michael S. Samuel, Grant R Wickman, Wickman, Grant R, Samuel, Michael S, Lochhead, Pamela A, and Olson, Michael F

Subjects
Stress fiber, RHOA, Rho kinases, biology, Chemistry, Kinase, Cancer, Actin cytoskeleton, medicine.disease, Cell biology, cell motility and migration, ROCK, biology.protein, medicine, cancer, Cytoskeleton, Rho-associated protein kinase, Actin
Abstract

The Rho-associated protein kinases ROCK I and ROCK II are central effectors for the RhoA, B, and C small molecular weight GTP-binding proteins, and promote actin-filament stabilization as well as actin-myosin contractility. The effects of ROCK on actin filaments initiate changes in cytoskeletal structure and organization that are critical for many physiological and pathological processes. ROCK has been functionally associated with cell cycle control and proliferation, survival and apoptosis, as well as cell motility and migration. Interestingly, regulation of each of these biological process may be significantly altered in tumor cells, resulting in the promotion of cancer progression. Extensive clinical and preclinical investigations provide evidence supportive of a role for ROCK in multiple aspects of cancer, and pharmacological ROCK inhibitors have been developed as potential anticancer chemotherapeutic agents. This chapter reviews the structure and function of ROCK I and ROCK II, with a particular focus on their potential roles in cancer.

Published
2010

123. Tissue selective expression of conditionally-regulated ROCK by gene targeting to a defined locus

Author

David Stevenson, Michael F. Olson, Michael S. Samuel, Sheila Bryson, June Munro, Stephen Forrow, Samuel, Michael S, Munro, June, Bryson, Sheila, Forrow, Stephen, Stevenson, David, and Olson, Michael F

Subjects
Hypoxanthine Phosphoribosyltransferase, skin, Genetic Vectors, Embryoid body, macromolecular substances, Biology, Polymerase Chain Reaction, Gene Expression Regulation, Enzymologic, follicle, Mice, Exon, Endocrinology, Rho, Genetics, Transcriptional regulation, mER™ [ROCKII], Animals, Humans, Promoter Regions, Genetic, Cells, Cultured, Embryonic Stem Cells, mouse, DNA Primers, Recombination, Genetic, Regulation of gene expression, rho-Associated Kinases, Base Sequence, Kinase, Keratin-14, Gene targeting, rock, Exons, Cell Biology, Immunohistochemistry, Molecular biology, Tamoxifen, Gene Targeting, Homologous recombination, actin, Minigene
Abstract

ROCK kinases regulate actin-myosin structures downstream of Rho GTPases. We generated mice expressing 4-hydroxytamoxifen (4HT)-regulated human ROCK II (ROCKII:mER) under the transcriptional control of the cytokeratin14 (K14) promoter. The K14-ROCKII: mER minigene was recombineered into a novel cloning vector containing the promoter and first exon of the human HPRT gene, and second and third exons of the mouse Hprt gene. Homologous recombination into the Hprt locus, which is deleted for the promoter and first two exons in HM1 embryonic stem cells, reconstitutes a functional Hprt gene, allowing for growth in HAT (hypoxanthine-aminopterin-thymidine) medium. K14-promoter-driven ROCKII:mER expression was restricted to a superficial cell layer in embryoid bodies, with increased ROCK substrate phosphorylation induced by 4HT. ROCKII:mER-expressing primary murine keratinocytes responded to 4HT with increased substrate phosphorylation and cytoskeleton rearrangements, indicating that ROCKII:mER activity is regulated by 4HT in the target tissue. K14-ROCKII:mER mice will be valuable for examining the role of ROCK in skin development and cancer. Refereed/Peer-reviewed

Published
2009

124. Elevated Dnmt3a activity promotes polyposis in Apc(Min) mice by relaxing extracellular restraints on Wnt signaling

Author

Joan K. Heath, Matthias Ernst, Niall C. Tebbutt, Paul M. Waring, Aliki Christou, Tracy L Putoczki, Melissa Inglese, Robyn L. Ward, Michael S. Samuel, Minoru Toyota, Hiromu Suzuki, Therese Lundgren-May, Michael Buchert, Samuel, Michael S, Suzuki, Hiromu, Buchert, Michael, Putoczki, Tracy L, Tebbutt, Niall C, Lundgren-May, Therese, Christou, Aliki, Inglese, Melissa, Toyota, Minoru, Heath, Joan K, WARD, Robyn L, Waring, Paul M, and Ernst, Matthias

Subjects
Genes, APC, Adenomatous polyposis coli, Transgene, Loss of Heterozygosity, colorectal cancer, Mice, Transgenic, medicine.disease_cause, DNA Methyltransferase 3A, epigenetic inactivation, Dnmt overexpression, Mice, Intestinal mucosa, AXIN2, medicine, Gene silencing, Animals, DNA (Cytosine-5-)-Methyltransferases, Gene Knock-In Techniques, Gene Silencing, Intestinal Mucosa, Cells, Cultured, Regulation of gene expression, DNA methylation, Membrane Glycoproteins, Hepatology, biology, Gastroenterology, Wnt signaling pathway, Mice, Mutant Strains, Gene Expression Regulation, Neoplastic, Wnt Proteins, cell-lines, Adenomatous Polyposis Coli, embryonic structures, biology.protein, Cancer research, Carcinogenesis, Signal Transduction
Abstract

Background & Aims Aberrant DNA methylation is a common early event in neoplasia, but it is unclear how this relates to dysregulation of DNA (cytosine-5) methyltransferases (Dnmts). Here we use knock-in transgenic mice to investigate the consequences of intestinal epithelium-specific overexpression of de novo Dnmt3a. Methods A novel gene targeting strategy, based on the intestinal epithelium-specific, uniform expression of the A33 glycoprotein, is employed to restrict Dnmt3a overexpression in homozygous A33 Dnmt3a mutant mice. Results A33 Dnmt3a mice infrequently develop spontaneous intestinal polyps. However, when genetically challenged, tumor multiplicity in A33 Dnmt3a ; Apc Min compound mice is 3-fold higher than in Apc Min mice. Although we observe a requirement for spontaneous loss of heterozygosity of the adenomatous polyposis coli ( Apc ) gene to trigger tumorigenesis in Apc Min mice, lesions in A33 Dnmt3a ; Apc Min mice frequently retain the wild-type Apc allele. However, epithelia from normal mucosa and polyps of A33 Dnmt3a ; Apc Min mice show hypermethylation-mediated transcriptional silencing of the Wnt antagonists Sfrp5 , and to a lesser extent, Sfrp1 and increased nuclear β-catenin alongside activation of the Wnt-target gene Axin2/Conductin . Conversely, enforced Sfrp5 expression suppresses canonical Wnt-signaling more effectively in wild-type than in Apc Min cells. Conclusions Aberrant activation of the canonical Wnt pathway, either by mono-allelic Apc loss or transcriptional silencing of Sfrp5 is largely insufficient to promote polyposis, but epistatic interactions between these genetic and epigenetic events enables initiation and promotion of disease. This mechanism is likely to play a role in human colorectal cancer, because we also show that elevated DNMT3A expression coincides with repressed SFRP5 and enhanced AXIN2/CONDUCTIN expression in paired patient biopsies.

Published
2008

125. Role of the Escherichia coli glgX Gene in Glycogen Metabolism

Author

David Dauvillée, Michael S. Samuel, Lynette Rampling, Zhongyi Li, Isabelle S. Kinderf, Matthew K. Morell, Behjat Kosar-Hashemi, Steven G. Ball, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), CSIRO Plant Industry, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physiology and Metabolism, Amylopectin, medicine.disease_cause, Microbiology, Substrate Specificity, Glycogen debranching enzyme, 03 medical and health sciences, chemistry.chemical_compound, Glycogen phosphorylase, Dextrins, Escherichia coli, Glycogen branching enzyme, medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Glycogen synthase, Glucans, Molecular Biology, Gene, Sequence Deletion, 030304 developmental biology, 0303 health sciences, biology, Glycogen, 030306 microbiology, Futile cycle, Genetic Complementation Test, Glycogen Debranching Enzyme System, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], chemistry, Biochemistry, biology.protein
Abstract

A role for the Escherichia coli glgX gene in bacterial glycogen synthesis and/or degradation has been inferred from the sequence homology between the glgX gene and the genes encoding isoamylase-type debranching enzymes; however, experimental evidence or definition of the role of the gene has been lacking. Construction of E. coli strains with defined deletions in the glgX gene is reported here. The results show that the GlgX gene encodes an isoamylase-type debranching enzyme with high specificity for hydrolysis of chains consisting of three or four glucose residues. This specificity ensures that GlgX does not generate an extensive futile cycle during glycogen synthesis in which chains with more than four glucose residues are transferred by the branching enzyme. Disruption of glgX leads to overproduction of glycogen containing short external chains. These results suggest that the GlgX protein is predominantly involved in glycogen catabolism by selectively debranching the polysaccharide outer chains that were previously recessed by glycogen phosphorylase.

Published
2005

126. Barley sex6 mutants lack starch synthase IIa activity and contain a starch with novel properties

Author

Peter M. Chandler, Sadequr Rahman, Behjat Kosar-Hashemi, Mark Cmiel, Michael S. Samuel, Zhongyi Li, Matthew K. Morell, Ian L Batey, Alain Buléon, PhysicoChimie des Macromolécules (LPCM), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
Genetic Linkage, Starch, Amylopectin, Molecular Sequence Data, Mutant, Plant Science, Endosperm, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, chemistry.chemical_compound, Starch Synthase, Amylose, [SDV.GEN.GPL] Life Sciences [q-bio]/Genetics/Plants genetics, Genetics, Glycogen branching enzyme, Amino Acid Sequence, Plant Proteins, Base Sequence, Calorimetry, Differential Scanning, biology, food and beverages, Hordeum, Cell Biology, Phenotype, Biochemistry, chemistry, Mutation, Seeds, biology.protein, Hordeum vulgare, Crystallization, Starch synthase
Abstract

Analysis of barley shrunken grain mutants has identified lines with a novel high amylose starch phenotype. The causal mutation is located at the sex6 locus on chromosome 7H, suggesting the starch synthase IIa (ssIIa) gene as a candidate gene altered by the mutation. Consistent with this hypothesis, no evidence of SSIIa protein expression in either the starch granule or soluble fractions of the endosperm was found. Sequences of the starch synthase IIa gene, ssIIa, from three independent sex6 lines showed the presence of a stop codon preventing translation of the ssIIa transcript in each line. Perfect segregation of the starch phenotype with the presence of stop codons in the ssIIa gene was obtained, providing strong evidence for the lesion in the ssIIa gene being the causal mutation for the sex6 phenotype. The loss of SSIIa activity in barley leads to novel and informative phenotypes. First, a decrease in amylopectin synthesis to less than 20% of the wild-type levels indicates that SSIIa accounts for the majority of the amylopectin polymer elongation activity in barley. Secondly, in contrast to high amylose starches resulting from branching enzyme downregulation, the sex6 starches have a shortened amylopectin chain length distribution and a reduced gelatinisation temperature. Thirdly, the mutation leads to pleiotropic effects on other enzymes of the starch biosynthesis pathway, abolishing the binding of SSI, branching enzyme IIa and branching enzyme IIb to the starch granules of sex6 mutants, while not significantly altering their expression levels in the soluble fraction.

Published
2003

127. Actomyosin contractililty: Force power drives tumor growth

Author

Michael S. Samuel and Michael F. Olson

Subjects
rho-Associated Kinases, Skin Neoplasms, Mice, Transgenic, Actomyosin, Cell Biology, Biology, Microscopy, Atomic Force, Models, Biological, Power (physics), Cell biology, Mice, Animals, Tumor growth, Collagen, Stress, Mechanical, Phosphorylation, rhoA GTP-Binding Protein, Molecular Biology, beta Catenin, Signal Transduction, Developmental Biology
Published
2011
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128. Abstract 930: Inducible ROCK 2/rasHa cooperation requires wound promotion to achieve malignancy in transgenic mouse skin carcinogenesis, whereas inducible ROCK 2/PTEN loss fails to achieve benign papilloma

Author

David A. Greenhalgh, Michael F. Olson, Siti Fathiah Masre, and Michael S. Samuel

Subjects
Genetically modified mouse, Cancer Research, Pathology, medicine.medical_specialty, integumentary system, biology, Oncogene, Transgene, Context (language use), Hyperplasia, medicine.disease, medicine.disease_cause, Oncology, medicine, Cancer research, biology.protein, Papilloma, PTEN, Carcinogenesis
Abstract

To study tumour progression mechanism in vivo, ROCK 2 signalling deregulation and co-operation with activated rasHa or PTEN loss was investigated in transgenic mouse skin carcinogenesis. Transgenic mice that expressed a 4-hydroxytamoxifen (4HT)-activated human ROCK 2-estrogen receptor fusion transgene from a keratin 14 promoter [K14.ROCKer] were crossed to mice expressing activated rasHa exclusively in epidermal transit amplifying keratinocytes [HK1.ras-ROCKer] or mice where cutaneous PTEN loss was achieved in basal layers, hair follicles and stem cell keratinocytes via topical RU486 treatment of bi-genic K14.creP/Δ5PTENflx genotypes [K14.Δ5PTEN-ROCKer]. Initial 4HT-treatments of K14.ROCKer mice [3/wk; 26 wks] induced epidermal and follicular hyperplasia but no papillomas; whilst treatment of HK1.ras line 1205 gave ear tag papillomas [10-12 wks] typically smaller than vehicle controls, but no malignant conversion. In contrast, 4-HT treated HK1.ras-Rocker papillomas [10-12 wks] exhibited areas of carcinoma in situ and well-differentiated squamous cell carcinoma [wdSCC]. With time [16-20wks] wdSCC areas increased, concomitant with loss of p53, increased p-AKT and altered differentiation marker expression; however histotypes remained wdSCC despite continued 4HT-induced Rock 2 activity; as confirmed by downstream MYPT-1 phosphorylation. Furthermore, papillomas regressed whenever 4-HT treated HK1.ras-Rocker mice lost ear tags, suggesting that continued promotion from wounding during papillomatogenesis was critical to achieving the appropriate [late-stage] papilloma context that facilitated Rock 2-mediated conversion. To test this idea, K14.ROCKer mice were crossed to HK1.ras line 1276, which is insensitive to wound promotion, and such bi-genic mice did not exhibit papillomas; while in reverse, demonstrating the need for initiation, classic TPA-promoted K14.ROCKer mice were also devoid of papillomas. In addition, as previously rasHa/PTENnull mice exhibited papillomas prone to conversion on acquisition of an additional oncogene [e.g. fos], K14.ROCKer mice were bred into a K14.cre.Δ5PTEN strain and bi-genic mice treated with Ru486 [3wks] and 4HT [>26wks]. Again, in the absence of rasHa no papillomas were observed and mice exhibited increased hyperplasia and altered differentiation consistent with disruption of epidermal physiology. These data suggest that Rock 2 deregulation plays major roles in malignant conversion and progression, and in cooperation with rasHa activation or PTEN loss, the mechanism requires additional promotion/initiation events during papillomatogenesis to create the context of late-stage papilloma where Rock 2 activities become causal; an idea being tested in tri-genic HK1.ras/Δ5PTEN-Rocker genotypes. Citation Format: Siti F. Masre, Michael S. Samuel, Michael F. Olson, David A. Greenhalgh. Inducible ROCK 2/rasHa cooperation requires wound promotion to achieve malignancy in transgenic mouse skin carcinogenesis, whereas inducible ROCK 2/PTEN loss fails to achieve benign papilloma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 930. doi:10.1158/1538-7445.AM2014-930

Published
2014
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129. Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation

Author

Nicholas Hauschild, Paul H. Anderson, Philip A. Gregory, Houng Taing, Kwok Ho Yip, Michael S. Samuel, Stephen J. Galli, Chunping Yu, David Goltzman, Natasha Kolesnikoff, Angel F. Lopez, Lisa Biggs, and Michele A. Grimbaldeston

Subjects
medicine.medical_specialty, biology, Chemistry, Immunology, Degranulation, Inflammation, Mast cell, Immunoglobulin E, Calcitriol receptor, Proinflammatory cytokine, Cell biology, medicine.anatomical_structure, Endocrinology, Mediator, Internal medicine, medicine, Vitamin D and neurology, biology.protein, Immunology and Allergy, medicine.symptom
Abstract

Background Mast cells have gained notoriety based on their detrimental contributions to IgE-mediated allergic disorders. Although mast cells express the vitamin D receptor (VDR), it is not clear to what extent 1α,25-dihydroxyvitamin D 3 (1α,25[OH] 2 D 3 ) or its predominant inactive precursor metabolite in the circulation, 25-hydroxyvitamin D 3 (25OHD 3 ), can influence IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo . Objective We sought to assess whether the vitamin D 3 metabolites 25OHD 3 and 1α,25(OH) 2 D 3 can repress IgE-dependent mast cell activation through mast cell–25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) and mast cell–VDR activity. Methods We measured the extent of vitamin D 3 suppression of IgE-mediated mast cell degranulation and mediator production in vitro , as well as the vitamin D 3 –induced curtailment of PCA responses in WBB6F 1 - Kit W/W-v or C57BL/6J- Kit W-sh/W-sh mice engrafted with mast cells that did or did not express VDR or CYP27B1. Results Here we show that mouse and human mast cells can convert 25OHD 3 to 1α,25(OH) 2 D 3 through CYP27B1 activity and that both of these vitamin D 3 metabolites suppressed IgE-induced mast cell–derived proinflammatory and vasodilatory mediator production in a VDR-dependent manner in vitro . Furthermore, epicutaneously applied vitamin D 3 metabolites significantly reduced the magnitude of skin swelling associated with IgE-mediated PCA reactions in vivo ; a response that required functional mast cell–VDRs and mast cell–CYP27B1. Conclusion Taken together, our findings provide a mechanistic explanation for the anti-inflammatory effects of vitamin D 3 on mast cell function by demonstrating that mast cells can actively metabolize 25OHD 3 to dampen IgE-mediated mast cell activation in vitro and in vivo .

Published
2014
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130. Dying Alone: A Tale of Rho

Author

Michael F. Olson and Michael S. Samuel

Subjects
Contractility, medicine.anatomical_structure, Apoptosis, Cell, medicine, Genetics, Molecular Medicine, Cell Biology, Stem cell, Biology, Embryonic stem cell, In vitro, Cell biology
Abstract

In this issue of Cell Stem Cell, Chen et al. (2010) and Ohgushi et al. (2010) report that Rho-mediated actomyosin contractility underlies the proclivity of human embryonic stem cells to undergo apoptosis upon dissociation or during low-density propagation, a property that challenges their in vitro isolation and manipulation.

Published
2010
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131. A complex arrangement of genes at a starch branching enzyme I locus in the D-genome donor of wheat

Author

Sadequr Rahman, S. Abrahams, R. Appels, David Abbott, Michael S. Samuel, Matthew K. Morell, and Yasuhiko Mukai

Subjects
DNA, Plant, Molecular Sequence Data, Locus (genetics), In situ hybridization, Biology, Genes, Plant, Genome, Polymerase Chain Reaction, chemistry.chemical_compound, Exon, Complementary DNA, 1,4-alpha-Glucan Branching Enzyme, Genetics, Amino Acid Sequence, Molecular Biology, Gene, In Situ Hybridization, Fluorescence, Triticum, Gene Library, Plant Proteins, Sequence Homology, Amino Acid, food and beverages, Chromosome Mapping, General Medicine, genomic DNA, chemistry, Sequence Alignment, DNA, Biotechnology
Abstract

Genomic DNA fragments from Triticum tauschii (D-genome donor to wheat) carrying starch branching enzyme I (SBE I) type genes have been characterized. One fragment contains one complete gene and two partial genes in 16 kb of DNA. One of the partial genes is oriented in the opposite strand to the other two. The gene that is complete was sequenced. Its structure corresponds closely to that of rice in that exons 3–8 are retained at similar sizes and spacings. A cDNA closely corresponding to the complete gene was isolated and characterized; it codes for a putative protein that represents a novel type of SBE I, as it is shorter at the 3′ end than the forms reported so far in other plants. A second genomic fragment contains a different SBE I gene. There appear to be approximately 10 copies of SBE I type genes in wheat (approximately 5 in T. tauschii) and most of them have been assigned to group 7 chromosomes. In situ hybridization indicates that a major locus for the genes is located at the distal end of the short arm of chromosome 7D.Key words: starch, branching enzyme genes, wheat, Triticum tauschii, in situ hybridization.

Published
1997

132. Differential expression and properties of starch branching enzyme isoforms in developing wheat endosperm

Author

Behjat Kosar-Hashemi, Andreas Blennow, Michael S. Samuel, and Matthew K. Morell

Subjects
Gene isoform, Physiology, Starch, Molecular Sequence Data, Plant Science, Isozyme, Gene Expression Regulation, Enzymologic, Endosperm, Substrate Specificity, chemistry.chemical_compound, Amylose, Gene Expression Regulation, Plant, 1,4-alpha-Glucan Branching Enzyme, Glycosyltransferase, Genetics, Poaceae, Amino Acid Sequence, Triticum, chemistry.chemical_classification, biology, food and beverages, Chromosome Mapping, Isoenzymes, Kinetics, Enzyme, chemistry, Biochemistry, biology.protein, Research Article
Abstract

Three forms of starch branching enzyme (BE) from developing hexaploid wheat (Triticum aestivum) endosperm have been partially purified and characterized. Immunological cross-reactivities indicate that two forms (WBE-IAD, 88 kD, and WBE-IB, 87 kD) are related to the maize BE I class and that WBE-II (88 kD) is related to maize BE II. Comparison of the N-terminal sequences from WBE-IAD and WBE-II with maize and rice BEs confirms these relationships. Evidence is presented from the analysis of nullisomic-tetrasomic wheat lines demonstrating that WBE-IB is located on chromosome 7B and that the WBE-IAD fraction contains polypeptides that are encoded on chromosomes 7A and 7D. The wheat endosperm BE classes are differentially expressed during endosperm development. WBE-II is expressed at a constant level throughout mid and late endosperm development. In contrast, WBE-IAD and WBE-IB are preferentially expressed in late endosperm development. Differences are also observed in the kinetic characteristics of the enzymes. The WBE-I isoforms have a 2- to 5-fold higher affinity for amylose than does WBE-II, and the WBE-I isoforms are activated up to 5-fold by phosphorylated intermediates and inorganic phosphate, whereas WBE-II is activated only 50%. The potential implications of this activation of BE I for starch biosynthesis are discussed.

Published
1997

134. The Major Proteins of Wheat Endosperm Starch Granules

Author

Jack Preiss, John H. Skerritt, Behjat Kosar-Hashemi, A. Hill, Michael S. Samuel, Matthew K. Morell, Rudi Appels, Sadequr Rahman, and David Abbott

Subjects
Gel electrophoresis, Molecular mass, Starch, Granule (cell biology), food and beverages, Plant Science, Biology, Proteinase K, Molecular biology, Endosperm, chemistry.chemical_compound, chemistry, Biochemistry, biology.protein, Glycogen branching enzyme, Starch synthase, Agronomy and Crop Science
Abstract

Wheat starch contains two classes of associated proteins: proteins which are embedded within the granule and loosely associated surface proteins. The characterisation of the major proteins that are embedded in the granule are described. Gel electrophoresis on the basis of size resolved these proteins into five bands of molecular weights 60, 75, 85, 100 and 105 kDa. These polypeptides were demonstrated to be within the granule by their resistance to proteinase K digestion when granules were ungelatinised. The N-terminal sequences of these polypeptides are reported. The most prominent polypeptide is the 60 kDa granule-bound starch synthase. The N-terminal sequence obtained from the 75 kDa polypeptide shows homology to rice soluble starch synthase. The 85 kDa band was resolved into at least two types of polypeptides, one of which reacted with polyclonal antiserum to the maize branching enzyme IIb. The 100 and 105 kDa polypeptides were located only in the granule and are related, on the basis of N-terminal sequence similarity and cross-reactivity to monoclonal antibodies. SDS-PAGE and monoclonal antibody cross-reactivity experiments suggest that the 100 and 105 kDa polypeptides are absent from starch granules from all other species examined, including other cereals. It is speculated that all the major granule proteins are involved in starch biosynthesis.

Published
1995
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135. A Negative Regulatory Mechanism Involving 14-3-3ζ Limits Signaling Downstream of ROCK to Regulate Tissue Stiffness in Epidermal Homeostasis

Author

Paul Timpson, Kaitlin G. Scheer, Lena Wullkopf, Stuart M. Pitson, Natasha Kolesnikoff, Frank C. Stomski, Michael S. Samuel, Jasreen Kular, Amr H. Allam, Joanna M. Woodcock, Anthony N. Pollard, Rebecca L. Wright, Paul A.B. Moretti, Angel F. Lopez, Hayley S. Ramshaw, Allison J. Cowin, Natasha T. Pyne, Michele A. Grimbaldeston, Astrid Magenau, Kular, Jasreen, Scheer, Kaitlin G, Pyne, Natasha T, Allam, Amr H, Pollard, Anthony N., Magenau, Astrid, Wright, Rebecca L, Kolesnikoff, Natasha, Moretti, Paul A, Wullkopf, Lena, Stomski, Frank C, Cowin, Allison J, Woodcock, Joanna M, Grimbaldeston, Michele A, Pitson, Stuart M, Timpson, Paul, Ramshaw, Hayley S, Lopez, Angel F, and Samuel, Michael S

Subjects
RHOA, Cell, RhoC, wound healing, General Biochemistry, Genetics and Molecular Biology, mechano-transduction, 14-3-3ζ, MYPT, Mice, ROCK, medicine, Animals, Homeostasis, re-epithelialization, Molecular Biology, Cell Proliferation, rho-Associated Kinases, biology, Epidermis (botany), integumentary system, Cell growth, RhoA, Anatomy, Cell Biology, Cell biology, medicine.anatomical_structure, 14-3-3 Proteins, biology.protein, mechano-reciprocity, Signal transduction, Epidermis, Wound healing, Signal Transduction, Developmental Biology
Abstract

ROCK signaling causes epidermal hyper-proliferation by increasing ECM production, elevating dermal stiffness, and enhancing Fak-mediated mechanotransduction signaling. Elevated dermal stiffness in turn causes ROCK activation, establishing mechano- reciprocity, a positive feedback loop that can promote tumors. We have identified a negative feedback mechanism that limits excessive ROCK signaling during wound healing and is lost in squamous cell carcinomas (SCCs). Signal flux through ROCK was selectively tuned down by increased levels of 14-3-3 zeta, which interacted with Mypt1, a ROCK signaling antagonist. In 14-3-3 zeta(-/-) mice, unrestrained ROCK signaling at wound margins elevated ECM production and reduced ECM remodeling, increasing dermal stiffness and causing rapid wound healing. Conversely, 14-3-3 zeta deficiency enhanced cutaneous SCC size. Significantly, inhibiting 14-33 zeta with a novel pharmacological agent accelerated wound healing 2-fold. Patient samples of chronic non-healing wounds overexpressed 14-3-3 zeta, while cutaneous SCCs had reduced 14-3-3 zeta. These results reveal a novel 14-3-3 zeta-dependent mechanism that negatively regulates mechano-reciprocity, suggesting new therapeutic opportunities. Refereed/Peer-reviewed

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136. Desmoglein-2 as a cancer modulator: friend or foe?

Author

Kay K. Myo Min, Charlie B. Ffrench, Barbara J. McClure, Michael Ortiz, Emma L. Dorward, Michael S. Samuel, Lisa M. Ebert, Mỹ G. Mahoney, and Claudine S. Bonder

Subjects
desmoglein-2 (DSG2), cancer, cadherin, intercellular junctions, prognostic biomarker, vasculogenic mimicry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological functions of DSG2 holds promise to exploit this cell surface protein as a potential prognostic biomarker and/or target for better patient outcomes. This review explores the canonical and non-canonical functions of DSG2, as well as the context-dependent impacts of DSG2 in the realm of cancer.

Published
2023
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