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The neurite outgrowth multiadaptor RhoGAP, NOMA-GAP, regulates neurite extension through SHP2 and Cdc42

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Item Type:Article
Title:The neurite outgrowth multiadaptor RhoGAP, NOMA-GAP, regulates neurite extension through SHP2 and Cdc42
Creators Name:Rosario, M. and Franke, R. and Bednarski, C. and Birchmeier, W.
Abstract:Neuronal differentiation involves the formation and extension of neuronal processes. We have identified a novel regulator of neurite formation and extension, the neurite outgrowth multiadaptor, NOMA-GAP, which belongs to a new family of multiadaptor proteins with RhoGAP activity. We show that NOMA-GAP is essential for NGF-stimulated neuronal differentiation and for the regulation of the ERK5 MAP kinase and the Cdc42 signaling pathways downstream of NGF. NOMA-GAP binds directly to the NGF receptor, TrkA, and becomes tyrosine phosphorylated upon receptor activation, thus enabling recruitment and activation of the tyrosine phosphatase SHP2. Recruitment of SHP2 is required for the stimulation of neuronal process extension and for sustained activation of ERK5 downstream of NOMA-GAP. In addition, we show that NOMA-GAP promotes neurite outgrowth by tempering activation of the Cdc42/PAK signaling pathway in response to NGF. NOMA-GAP, through its dual function as a multiadaptor and RhoGAP protein, thus plays an essential role downstream of NGF in promoting neurite outgrowth and extension.
Keywords:cdc42 GTP-Binding Protein, Cell Differentiation, Enzyme Activation, GTPase-Activating Proteins, Mitogen-Activated Protein Kinase 7, Nerve Growth Factor, Neurites, NIH 3T3 Cells, Non-Receptor Type 11 Protein Tyrosine Phosphatase, p21-Activated Kinases, PC12 Cells, Signal Transducing Adaptor Proteins, Signal Transduction, Small Interfering RNA, Two-Hybrid System Techniques, Animals, Mice, Rats
Source:Journal of Cell Biology
Publisher:Rockefeller University Press
Page Range:503-516
Date:30 July 2007
Additional Information:Copyright (c) 2007 by Rockefeller University Press
Official Publication:https://doi.org/10.1083/jcb.200609146
PubMed:View item in PubMed

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