Article
- The EMBO Journal (2007) 26, 2029 - 2040
- doi:10.1038/sj.emboj.7601659
Published online: 22 March 2007
Subject Categories:
Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation
Melinda D Willard1,2,3, Francis S Willard1,2,3, Xiaoyan Li2, Steven D Cappell1, William D Snider2 and David P Siderovski1,2,3
- Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA
- UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
Correspondence to:
David P Siderovski, Department of Pharmacology, UNC-Chapel Hill School of Medicine, 1106 ME Jones Bldg, CB 7365, Manning Dr Chapel Hill, NC 27599-7365, USA. Tel.: +1 919 843 9363; Fax: +1 919 966 5640; E-mail: dsiderov@med.unc.edu
Received 17 August 2006; Accepted 27 February 2007
Abstract
Regulator of G-protein signaling (RGS) proteins accelerate GTP hydrolysis by heterotrimeric G-protein 
subunits and thus inhibit signaling by many G protein-coupled receptors. Several RGS proteins have a multidomain architecture that adds further complexity to their roles in cell signaling in addition to their GTPase-accelerating activity. RGS12 contains a tandem repeat of Ras-binding domains but, to date, the role of this protein in Ras-mediated signal transduction has not been reported. Here, we show that RGS12 associates with the nerve growth factor (NGF) receptor tyrosine kinase TrkA, activated H-Ras, B-Raf, and MEK2 and facilitates their coordinated signaling to prolonged ERK activation. RGS12 is required for NGF-mediated neurite outgrowth of PC12 cells, but not outgrowth stimulated by basic fibroblast growth factor. siRNA-mediated knockdown of RGS12 expression also inhibits NGF-induced axonal growth in dissociated cultures of primary dorsal root ganglia neurons. These data suggest that RGS12 may play a critical, and receptor-selective, role in coordinating Ras-dependent signals that are required for promoting and/or maintaining neuronal differentiation.
Keywords:
- MEK,
- Raf,
- Ras,
- RGS12,
- TrkA
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Coordinating ERK/MAPK signalling through scaffolds and inhibitors
Nature Reviews Molecular Cell Biology Review (01 Nov 2005)
NEWS AND VIEWS
Untangling the signalling wires
Nature Cell Biology News and Views (01 Mar 2007)
Signal transduction Taking the Rap
Nature News and Views (09 Apr 1998)
RESEARCH
Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo
Nature Neuroscience Article (01 May 2007)
The EMBO Journal Article (16 Jun 2004)
