Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways.

Authors: Shu, FJ  Ramineni, S  Hepler, JR 
Citation: Shu FJ, etal., Cell Signal. 2010 Mar;22(3):366-76. doi: 10.1016/j.cellsig.2009.10.005. Epub .
Pubmed: (View Article at PubMed) PMID:19878719
DOI: Full-text: DOI:10.1016/j.cellsig.2009.10.005

MAPkinase signalling is essential for cell growth, differentiation and cell physiology. G proteins and tyrosine kinase receptors each modulate MAPkinase signalling through distinct pathways. We report here that RGS14 is an integrator of G protein and MAPKinase signalling pathways. RGS14 contains a GPR/GoLoco (GL) domain that forms a stable complex with inactive Gialpha1/3-GDP, and a tandem (R1, R2) Ras binding domain (RBD). We find that RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells. Activated H-Ras binds RGS14 at the R1 RBD to form a stable complex at cell membranes. RGS14 also co-localizes with and forms a complex with Raf kinases in cells. The regulatory region of Raf-1 binds the RBD region of RGS14, and H-Ras and Raf each facilitate one another's binding to RGS14. RGS14 selectively inhibits PDGF-, but not EGF- or serum-stimulated Erk phosphorylation. This inhibition is dependent on H-Ras binding to RGS14 and is reversed by co-expression of Gialpha1, which binds and recruits RGS14 to the plasma membrane. Gialpha1 binding to RGS14 inhibits Raf binding, indicating that Gialpha1 and Raf binding to RGS14 are mutually exclusive. Taken together, these findings indicate that RGS14 is a newly appreciated integrator of G protein and Ras/Raf signalling pathways.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 8553779
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.