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Titolo:
ROLE OF C-SRC TYROSINE KINASE IN G PROTEIN-COUPLED RECEPTOR-MEDIATED AND G-BETA-GAMMA-SUBUNIT-MEDIATED ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES
Autore:
LUTTRELL LM; HAWES BE; VANBIESEN T; LUTTRELL DK; LANSING TJ; LEFKOWITZ RJ;
Indirizzi:
DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,BOX 3821 DURHAM NC 27710 DUKE UNIV,MED CTR,HOWARD HUGHES MED INST DURHAM NC 27710 DUKE UNIV,MED CTR,DEPT MED DURHAM NC 27710 DUKE UNIV,MED CTR,DEPT BIOCHEM DURHAM NC 27710 GLAXO WELLCOME INC,DEPT MOL CELL BIOL RES TRIANGLE PK NC 27709
Titolo Testata:
The Journal of biological chemistry
fascicolo: 32, volume: 271, anno: 1996,
pagine: 19443 - 19450
SICI:
0021-9258(1996)271:32<19443:ROCTKI>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; HETEROTRIMERIC G-PROTEINS; DOMINANT-NEGATIVE MUTANT; GROWTH-FACTOR RECEPTOR; SHC ADAPTER PROTEIN; LYSOPHOSPHATIDIC ACID; MAP KINASE; SIGNALING PATHWAYS; PHOSPHOINOSITIDE-3 KINASE; ANGIOTENSIN-II;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
57
Recensione:
Indirizzi per estratti:
Citazione:
L.M. Luttrell et al., "ROLE OF C-SRC TYROSINE KINASE IN G PROTEIN-COUPLED RECEPTOR-MEDIATED AND G-BETA-GAMMA-SUBUNIT-MEDIATED ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES", The Journal of biological chemistry, 271(32), 1996, pp. 19443-19450

Abstract

Several G protein-coupled receptors that interact with pertussis toxin-sensitive heterotrimeric G proteins mediate Ras-dependent activationof mitogen-activated protein (MAP) kinases, The mechanism involves G beta gamma subunit-mediated increases in tyrosine phosphorylation of the She adapter protein, Shc-Grb2 complex formation, and recruitment ofPas guanine nucleotide exchange factor activity. We have investigatedthe role of the ubiquitous nonreceptor tyrosine kinase c-Src in activation of the MAP kinase pathway via endogenous G protein-coupled lysophosphatidic acid (LPA) receptors or by transient expression of G beta gamma subunits in COS-7 cells. In vitro kinase assays of She immunoprecipitates following LPA stimulation demonstrated rapid, transient recruitment of tyrosine kinase activity into She immune complexes, Recruitment of tyrosine kinase activity was pertussis toxin sensitive and mimicked by cellular expression of G beta gamma subunits. Immunoblots forcoprecipitated proteins in She immunoprecipitates revealed a transient association of Shc and c-Src following LPA stimulation, which coincided with increases in Shc-associated tyrosine kinase activity and She tyrosine phosphorylation. LPA stimulation or expression of G beta gamma subunits resulted in c-Src activation, as assessed by increased c-Src autophosphorylation, Overexpression of wild-type or constitutively active mutant c-Src, but not kinase inactive mutant c-Src, lead to increased tyrosine kinase activity in She immunoprecipitates, increased She tyrosine phosphorylation, and Shc-Grb2 complex formation, MAP kinaseactivation resulting from LPA receptor stimulation, expression of G beta gamma subunits, or expression of c-Src was sensitive to dominant negatives of mSos, Pas, and Raf. Coexpression of Csk, which inactivatesSrc family kinases by phosphorylating the regulatory C-terminal tyrosine residue, inhibited LPA stimulation of Shc tyrosine phosphorylation, Shc-Grb2 complex formation, and MAP kinase activation, These data suggest that G beta gamma subunit-mediated formation of Shc-c-Src complexes and c-Src kinase activation are early events in Ras-dependent activation of MAP kinase via pertussis toxin-sensitive G protein coupled receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 02:45:47