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Receptor protein tyrosine phosphatases are novel components of a polycystin complex.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2011 Oct; Vol. 1812 (10), pp. 1225-38. Date of Electronic Publication: 2010 Nov 29. - Publication Year :
- 2011
-
Abstract
- Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutation of PKD1 and PKD2 that encode polycystin-1 and polycystin-2. Polycystin-1 is tyrosine phosphorylated and modulates multiple signaling pathways including AP-1, and the identity of the phosphatases regulating polycystin-1 are previously uncharacterized. Here we identify members of the LAR protein tyrosine phosphatase (RPTP) superfamily as members of the polycystin-1complex mediated through extra- and intracellular interactions. The first extracellular PKD1 domain of polycystin-1 interacts with the first Ig domain of RPTPσ, while the polycystin-1 C-terminus of polycystin-1 interacts with the regulatory D2 phosphatase domain of RPTPγ. Additional homo- and heterotypic interactions between RPTPs recruit RPTPδ. The multimeric polycystin protein complex is found localised in cilia. RPTPσ and RPTPδ are also part of a polycystin-1/E-cadherin complex known to be important for early events in adherens junction stabilisation. The interaction between polycystin-1 and RPTPγ is disrupted in ADPKD cells, while RPTPσ and RPTPδ remain closely associated with E-cadherin, largely in an intracellular location. The polycystin-1 C-terminus is an in vitro substrate of RPTPγ, which dephosphorylates the c-Src phosphorylated Y4237 residue and activates AP1-mediated transcription. The data identify RPTPs as novel interacting partners of the polycystins both in cilia and at adhesion complexes and demonstrate RPTPγ phosphatase activity is central to the molecular mechanisms governing polycystin-dependent signaling. This article is part of a Special Issue entitled: Polycystic Kidney Disease.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Cadherins chemistry
Cadherins metabolism
Cell Line
Cell Membrane chemistry
Humans
In Vitro Techniques
Kidney metabolism
Mice
Models, Molecular
Multiprotein Complexes chemistry
Mutagenesis, Site-Directed
Peptide Library
Polycystic Kidney, Autosomal Dominant genetics
Polycystic Kidney, Autosomal Dominant metabolism
Protein Interaction Domains and Motifs
Receptor-Like Protein Tyrosine Phosphatases genetics
Receptor-Like Protein Tyrosine Phosphatases metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 2 chemistry
Receptor-Like Protein Tyrosine Phosphatases, Class 2 genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 2 metabolism
Receptor-Like Protein Tyrosine Phosphatases, Class 5 chemistry
Receptor-Like Protein Tyrosine Phosphatases, Class 5 genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 5 metabolism
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Signal Transduction
TRPP Cation Channels genetics
TRPP Cation Channels metabolism
Transcription Factor AP-1 metabolism
Receptor-Like Protein Tyrosine Phosphatases chemistry
TRPP Cation Channels chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1812
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 21126580
- Full Text :
- https://doi.org/10.1016/j.bbadis.2010.11.006