|c-Src is involved in regulating signal transmission from PDGFbeta receptor-GPCR(s) complexes in mammalian cells.|
|PMID: 15494217 Owner: NLM Status: MEDLINE|
|We have reported that the platelet-derived growth factor receptor-beta (PDGFbeta) forms a novel signaling complex with G protein-coupled receptors (GPCR) (e.g. S1P(1) receptor) that enables more efficient activation of p42/p44 mitogen-activated protein kinase (MAPK) in response to PDGF and sphingosine 1-phosphate (S1P). We now demonstrate that c-Src participates in regulating the endocytosis of PDGFbeta receptor-GPCR complexes in response to PDGF. This leads to association of cytoplasmic p42/p44 MAPK with the receptor complex in endocytic vesicles. c-Src is regulated by G protein betagamma subunits and can interact with beta-arrestin. Indeed, the PDGF-dependent activation of p42/p44 MAPK was reduced by over-expression of the C-terminal domain of GRK2 (sequesters Gbetagamma subunits), the clathrin-binding domain of beta-arrestin and by inhibitors of c-Src and clathrin-mediated endocytosis. Moreover, PDGF and S1P induce the recruitment of c-Src to the PDGFbeta receptor-S1P(1) receptor complex. This leads to a G protein/c-Src-dependent tyrosine phosphorylation of Gab1 and accumulation of dynamin II at the plasma membrane, a step required for endocytosis of the PDGFbeta receptor-GPCR complex. These findings provide important information concerning the molecular organisation of novel receptor tyrosine kinase (RTK)-GPCR signal relays in mammalian cells.|
|Catherine M Waters; Michelle C Connell; Susan Pyne; Nigel J Pyne|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Cellular signalling Volume: 17 ISSN: 0898-6568 ISO Abbreviation: Cell. Signal. Publication Date: 2005 Feb|
|Created Date: 2004-10-20 Completed Date: 2005-04-26 Revised Date: 2009-11-19|
Medline Journal Info:
|Nlm Unique ID: 8904683 Medline TA: Cell Signal Country: England|
|Languages: eng Pagination: 263-77 Citation Subset: IM|
|Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor St., Glasgow G4 ONR, UK.|
|APA/MLA Format Download EndNote Download BibTex|
Adaptor Proteins, Signal Transducing / genetics, metabolism
Arrestins / genetics, metabolism
Cadaverine / analogs & derivatives*, pharmacology
Concanavalin A / pharmacology
Cyclic AMP-Dependent Protein Kinases / genetics, metabolism
Dynamin II / metabolism
Endocytosis / drug effects
Enzyme Inhibitors / pharmacology
GRB2 Adaptor Protein
Lysophospholipids / pharmacology
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Myocytes, Smooth Muscle / drug effects, metabolism, physiology
Pertussis Toxin / pharmacology
Phosphoproteins / metabolism
Phosphorylation / drug effects
Platelet-Derived Growth Factor / pharmacology
Proto-Oncogene Proteins pp60(c-src) / metabolism, physiology*
Pyrimidines / pharmacology
Receptor, Platelet-Derived Growth Factor beta / genetics, metabolism, physiology*
Receptors, G-Protein-Coupled / genetics, metabolism, physiology*
Receptors, Lysosphingolipid / genetics, metabolism
Signal Transduction / drug effects, physiology*
Sphingosine / analogs & derivatives*, pharmacology
Transport Vesicles / chemistry, metabolism
beta-Adrenergic Receptor Kinases
|0/AG 1879; 0/Adaptor Proteins, Signal Transducing; 0/Arrestins; 0/Enzyme Inhibitors; 0/GAB1 protein, human; 0/GRB2 Adaptor Protein; 0/GRB2 protein, human; 0/Lysophospholipids; 0/Phosphoproteins; 0/Platelet-Derived Growth Factor; 0/Pyrimidines; 0/Receptors, G-Protein-Coupled; 0/Receptors, Lysosphingolipid; 0/beta-arrestin; 10121-91-2/monodansylcadaverine; 11028-71-0/Concanavalin A; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; 462-94-2/Cadaverine; EC 22.214.171.124/Pertussis Toxin; EC 126.96.36.199/1-Phosphatidylinositol 3-Kinase; EC 188.8.131.52/Receptor, Platelet-Derived Growth Factor beta; EC 184.108.40.206/Proto-Oncogene Proteins pp60(c-src); EC 220.127.116.11/Cyclic AMP-Dependent Protein Kinases; EC 18.104.22.168/beta-Adrenergic Receptor Kinases; EC 22.214.171.124/Mitogen-Activated Protein Kinase 1; EC 126.96.36.199/Mitogen-Activated Protein Kinase 3; EC 188.8.131.52/Dynamin II|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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