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Ras-related C3 Botulinum Toxin Substrate (Rac) and Src Family Kinases (SFK) Are Proximal and Essential for Phosphatidylinositol 3-Kinase (PI3K) Activation in Natural Killer (NK) Cell-mediated Direct Cytotoxicity against Cryptococcus neoformans.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2016 Mar 25; Vol. 291 (13), pp. 6912-22. Date of Electronic Publication: 2016 Feb 11. - Publication Year :
- 2016
-
Abstract
- The activity of Rac in leukocytes is essential for immunity. However, its role in NK cell-mediated anti-microbial signaling remains unclear. In this study, we investigated the role of Rac in NK cell mediated anti-cryptococcal killing. We found thatCryptococcus neoformansindependently activates both Rac and SFK pathways in NK cells, and unlike in tumor killing,Cryptococcusinitiated a novel Rac → PI3K → Erk cytotoxicity cascade. Remarkably, Rac was not required for conjugate formation, despite its essential role in NK cytotoxicity againstC. neoformans Taken together, our data show that, unlike observations with tumor cells, NK cells use a novel Rac cytotoxicity pathway in conjunction with SFK, to killC. neoformans.<br /> (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Cell Line, Tumor
Class Ia Phosphatidylinositol 3-Kinase genetics
Gene Expression Regulation
Host-Pathogen Interactions
Humans
Killer Cells, Natural drug effects
Killer Cells, Natural microbiology
Mitogen-Activated Protein Kinase 1 genetics
Mitogen-Activated Protein Kinase 1 immunology
Mitogen-Activated Protein Kinase 3 genetics
Mitogen-Activated Protein Kinase 3 immunology
Phosphorylation drug effects
Primary Cell Culture
Pyrones pharmacology
Quinolines pharmacology
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
rac GTP-Binding Proteins antagonists & inhibitors
rac GTP-Binding Proteins genetics
rac1 GTP-Binding Protein antagonists & inhibitors
rac1 GTP-Binding Protein genetics
src-Family Kinases genetics
RAC2 GTP-Binding Protein
Class Ia Phosphatidylinositol 3-Kinase immunology
Cryptococcus neoformans physiology
Cytotoxicity, Immunologic
Killer Cells, Natural immunology
rac GTP-Binding Proteins immunology
rac1 GTP-Binding Protein immunology
src-Family Kinases immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 291
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26867574
- Full Text :
- https://doi.org/10.1074/jbc.M115.681544