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Transient Association of the Phosphotyrosine Phosphatase SHP‐2 with TrkA Is Induced by Nerve Growth Factor
Author(s) -
Goldsmith Bruce A.,
Koizumi Shinichi
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69031014.x
Subject(s) - tropomyosin receptor kinase a , nerve growth factor , protein tyrosine phosphatase , low affinity nerve growth factor receptor , phosphorylation , tyrosine phosphorylation , tyrosine , signal transduction , proto oncogene tyrosine protein kinase src , biology , microbiology and biotechnology , tyrosine kinase , endocrinology , receptor tyrosine kinase , dephosphorylation , medicine , receptor , chemistry , phosphatase , biochemistry
Nerve growth factor (NGF) treatment of rat PC12 pheochromocytoma cells results in an increase in the tyrosine phosphorylation of the NGF receptor, TrkA, leading to differentiation to a neuronal phenotype. Dephosphorylation by protein tyrosine phosphatases (PTPases) is thought to play an important role in regulating this signaling pathway. To identify PTPases that are recruited to the activated TrkA receptor, we used an ingel PTPase assay to examine the presence of PTPases in TrkA immunoprecipitates. The Src homology 2 domain containing PTPase SHP‐2 was found to associate transiently with TrkA following receptor activation, reaching a peak after 1 min of NGF treatment and then decreasing rapidly. The association of SHP‐2 with TrkA was accompanied by the tyrosine phosphorylation of SHP‐2 and an association of SHP‐2 with multiple tyrosine‐phosphorylated proteins. In addition, the PTPase activity in SHP‐2 immunoprecipitates increased greater than twofold after 1 min of NGF treatment. This is the first demonstration that the association of SHP‐2 with TrkA is induced by NGF and that this association leads to SHP‐2 activation and tyrosine phosphorylation. We conclude that SHP‐2 plays a significant role in early biochemical events in TrkA‐mediated signal transduction.