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The platelet-derived growth factor receptor stimulation of p42/p44 mitogen-activated protein kinase in airway smooth muscle involves a G-protein-mediated tyrosine phosphorylation of Gab1

Rakhit, Soma and Pyne, Susan and Pyne, Nigel J. (2000) The platelet-derived growth factor receptor stimulation of p42/p44 mitogen-activated protein kinase in airway smooth muscle involves a G-protein-mediated tyrosine phosphorylation of Gab1. Molecular Pharmacology, 58 (2). pp. 413-420. ISSN 0026-895X

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Abstract

Using cultured airway smooth muscle cells, we showed previously that the platelet-derived growth factor (PDGF) receptor uses the G-protein, G(i), to stimulate Grb-2-associated phosphoinositide 3-kinase (PI3K) activity. We also showed that this was an intermediate step in the activation of p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) by PDGF. We now present two lines of evidence that provide further support for this model. First, we report that PDGF stimulates the G(i)-mediated tyrosine phosphorylation of the Grb-2 adaptor protein, Gab1. This phosphorylation appears to be necessary for association of PI3K1a with the Gab1-Grb-2 complex. Second, PI3K appears to promote the subsequent association of dynamin II (which is involved in clathrin-mediated endocytic processing) with the complex. Furthermore, inhibitors of PI3K and clathrin-mediated endocytosis reduced the PDGF-dependent activation of p42/p44 MAPK, suggesting a role for PI3K in the endocytic signaling process leading to stimulation of p42/p44 MAPK. Together, these results begin to define a common signaling model for certain growth factor receptors (e.g., PDGF, insulin, insulin-like growth factor-1, and fibroblast growth factor) which use G(i) to transmit signals to p42/p44 MAPK.

Item type: Article
ID code: 34951
Keywords: animals, cells, cultured, dynamins, enzyme activation, GTP phosphohydrolases, GTP-binding protein alpha subunits, Gi-Go, GTP-binding proteins, guinea pigs, insulin receptor substrate proteins, mitogen-activated protein kinase 1, muscle, smooth, phosphatidylinositol 3-kinases, phosphoproteins, phosphorylation, receptors, platelet-derived growth factor, tyrosine, Therapeutics. Pharmacology, Molecular Medicine, Pharmacology
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences > Physiology and Pharmacology
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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Depositing user: Pure Administrator
Date Deposited: 15 Nov 2011 16:56
Last modified: 05 Sep 2014 12:36
URI: http://strathprints.strath.ac.uk/id/eprint/34951

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