Document Detail

c-SRC mediates neurite outgrowth through recruitment of Crk to the scaffolding protein Sin/Efs without altering the kinetics of ERK activation.
MedLine Citation:
PMID:  11867627     Owner:  NLM     Status:  MEDLINE    
SRC family kinases have been consistently and recurrently implicated in neurite extension events, yet the mechanism underlying their neuritogenic role has remained elusive. We report that epidermal growth factor (EGF) can be converted from a non-neuritogenic into a neuritogenic factor through moderate activation of endogenous SRC by receptor-protein-tyrosine phosphatase alpha (a physiological SRC activator). We show that such a qualitative change in the response to EGF is not accompanied by changes in the extent or kinetics of ERK induction in response to this factor. Instead, the pathway involved relies on increased tyrosine phosphorylation of, and recruitment of Crk to, the SRC substrate Sin/Efs. The latter is a scaffolding protein structurally similar to the SRC substrate Cas, tyrosine phosphorylation of which is critical for migration in fibroblasts and epithelial cells. Expression of a dominant negative version of Sin interfered with receptor-protein-tyrosine phosphatase alpha/EGF- as well as fibroblast growth factor-induced neurite outgrowth. These observations uncouple neuritogenic signaling in PC12 cells from sustained activation of ERK kinases and for the first time identify an effector of SRC function in neurite extension.
Liang-Tung Yang; Konstantina Alexandropoulos; Jan Sap
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2002-02-26
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-13     Completed Date:  2002-07-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17406-14     Citation Subset:  IM    
Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
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MeSH Terms
Enzyme Activation
Epidermal Growth Factor / metabolism
Fluorescent Antibody Technique
Genes, src / physiology*
Mitogen-Activated Protein Kinases / metabolism*
Neurites / physiology*
Neurons / physiology*
PC12 Cells
Protein Tyrosine Phosphatases / physiology*
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-crk
Receptor-Like Protein Tyrosine Phosphatases, Class 4
Receptors, Cell Surface*
Signal Transduction / physiology
Tyrosine / metabolism
src-Family Kinases / metabolism
Grant Support
Reg. No./Substance:
0/Crk protein, rat; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-crk; 0/Receptors, Cell Surface; 55520-40-6/Tyrosine; 62229-50-9/Epidermal Growth Factor; EC Kinases; EC Protein Kinases; EC Tyrosine Phosphatases; EC protein, rat; EC Protein Tyrosine Phosphatases, Class 4

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