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The guanine-nucleotide-exchange factor P-Rex1 is activated by protein phosphatase 1α.
- Source :
-
Biochemical Journal . 4/ 1/2012, Vol. 443 Issue 1, following p173-183. 14p. - Publication Year :
- 2012
-
Abstract
- P-Rex1 is a GEF (guanine-nucleotide-exchange factor) for the small G-protein Rac that is activated by PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and Gβγ subunits and inhibited by PKA (protein kinase A). In the present study we show that PP1α (protein phosphatase 1α) binds P-Rex1 through an RVxF-type docking motif. PP1α activates P-Rex1 directly in vitro, both independently of and additively to PIP3 and Gβγ . PP1α also substantially activates P-Rex1 in vivo, both in basal and PDGF (platelet-derived growth factor)- or LPA (lysophosphatidic acid)- stimulated cells. The phosphatase activity of PP1α is required for P-Rex1 activation. PP1β, a close homologue of PP1α, is also able to activate P-Rex1, but less effectively. PP1α stimulates P-Rex1- mediated Rac-dependent changes in endothelial cell morphology. MS analysis of wild-type P-Rex1 and a PP1α-binding-deficient mutant revealed that endogenous PP1α dephosphorylates P-Rex1 on at least three residues, Ser834, Ser1001 and Ser1165. Site-directed mutagenesis of Ser1165 to alanine caused activation of P-Rex1 to a similar degree as did PP1α, confirming Ser1165 as a dephosphorylation site important in regulating P-Rex1 Rac-GEF activity. In summary, we have identified a novel mechanism for direct activation of P-Rex1 through PP1α- dependent dephosphorylation [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02646021
- Volume :
- 443
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Biochemical Journal
- Publication Type :
- Academic Journal
- Accession number :
- 85624537
- Full Text :
- https://doi.org/10.1042/BJ20112078