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G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.

dc.contributor.author Hawes, BE
dc.contributor.author Lefkowitz, Robert J
dc.contributor.author Touhara, K
dc.contributor.author van Biesen, T
dc.coverage.spatial United States
dc.date.accessioned 2013-09-10T15:37:04Z
dc.date.issued 1995-09-26
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/7568118
dc.identifier.issn 0027-8424
dc.identifier.uri https://hdl.handle.net/10161/7837
dc.description.abstract The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, and an as-yet-unidentified tyrosine kinase. To investigate the mechanism of G beta gamma-stimulated p21ras activation, G beta gamma-mediated tyrosine phosphorylation was examined by overexpressing G beta gamma or alpha 2-C10 adrenergic receptors (ARs) that couple to Gi in COS-7 cells. Immunoprecipitation of phosphotyrosine-containing proteins revealed a 2- to 3-fold increase in the phosphorylation of two proteins of approximately 50 kDa (designated as p52) in G beta gamma-transfected cells or in alpha 2-C10 AR-transfected cells stimulated with the agonist UK-14304. The latter response was pertussis toxin sensitive. These proteins (p52) were also specifically immunoprecipitated with anti-Shc antibodies and comigrated with two Shc proteins, 46 and 52 kDa. The G beta gamma- or alpha 2-C10 AR-stimulated p52 (Shc) phosphorylation was inhibited by coexpression of the carboxyl terminus of beta-adrenergic receptor kinase (a G beta gamma-binding pleckstrin homology domain peptide) or by the tyrosine kinase inhibitors genistein and herbimycin A, but not by a dominant negative mutant of p21ras. Worthmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) inhibited phosphorylation of p52 (Shc), implying involvement of PI3K. These results suggest that G beta gamma-stimulated Shc phosphorylation represents an early step in the pathway leading to p21ras activation, similar to the mechanism utilized by growth factor tyrosine kinase receptors.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.subject Adaptor Proteins, Signal Transducing
dc.subject Adaptor Proteins, Vesicular Transport
dc.subject Androstadienes
dc.subject Animals
dc.subject Benzoquinones
dc.subject Calcium-Calmodulin-Dependent Protein Kinases
dc.subject Cell Line
dc.subject Cercopithecus aethiops
dc.subject Enzyme Activation
dc.subject Enzyme Inhibitors
dc.subject GTP-Binding Proteins
dc.subject Genistein
dc.subject Humans
dc.subject Isoflavones
dc.subject Kidney
dc.subject Kinetics
dc.subject Lactams, Macrocyclic
dc.subject Macromolecular Substances
dc.subject Pertussis Toxin
dc.subject Phosphates
dc.subject Phosphatidylinositol 3-Kinases
dc.subject Phosphorylation
dc.subject Phosphotransferases (Alcohol Group Acceptor)
dc.subject Protein-Tyrosine Kinases
dc.subject Proteins
dc.subject Proto-Oncogene Proteins p21(ras)
dc.subject Quinones
dc.subject Receptors, Adrenergic, alpha-2
dc.subject Recombinant Proteins
dc.subject Rifabutin
dc.subject Shc Signaling Adaptor Proteins
dc.subject Src Homology 2 Domain-Containing, Transforming Protein 1
dc.subject Tetradecanoylphorbol Acetate
dc.subject Transfection
dc.subject Virulence Factors, Bordetella
dc.title G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/7568118
pubs.begin-page 9284
pubs.end-page 9287
pubs.issue 20
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Chemistry
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 92


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