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Titolo:
REQUIREMENT OF PHOSPHOLIPASE C-GAMMA, THE TYROSINE PHOSPHATASE SYP AND THE ADAPTER PROTEINS SHC AND NCK FOR PDGF-INDUCED DNA-SYNTHESIS - EVIDENCE FOR THE EXISTENCE OF RAS-DEPENDENT AND RAS-INDEPENDENT PATHWAYS
Autore:
ROCHE S; MCGLADE J; JONES M; GISH GD; PAWSON T; COURTNEIDGE SA;
Indirizzi:
FAC PHARM MONTPELLIER,CJF9207 INSERM,AVE CH FLAHAUT F-34060 MONTPELLIER FRANCE EUROPEAN MOL BIOL LAB,DIFFERENTIAT PROGRAMME D-69012 HEIDELBERG GERMANY MT SINAI HOSP,SAMUEL LUNENFELD RES INST,PROGRAMME MOL BIOL & CANC TORONTO ON M5G 1X5 CANADA UNIV TORONTO,DEPT MED & MOL GENET TORONTO ON M5G 1X5 CANADA
Titolo Testata:
EMBO journal
fascicolo: 18, volume: 15, anno: 1996,
pagine: 4940 - 4948
SICI:
0261-4189(1996)15:18<4940:ROPCTT>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR RECEPTOR; MITOGENIC SIGNAL-TRANSDUCTION; SWISS 3T3 CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; BETA-RECEPTOR; MAP-KINASE; PHOSPHOTYROSINE PHOSPHATASE; AUTOPHOSPHORYLATION SITES; NEURONAL DIFFERENTIATION; LYSOPHOSPHATIDIC ACID;
Keywords:
DNA SYNTHESIS; PDGF RECEPTOR; RAS; SIGNALING; TYROSINE KINASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
S. Roche et al., "REQUIREMENT OF PHOSPHOLIPASE C-GAMMA, THE TYROSINE PHOSPHATASE SYP AND THE ADAPTER PROTEINS SHC AND NCK FOR PDGF-INDUCED DNA-SYNTHESIS - EVIDENCE FOR THE EXISTENCE OF RAS-DEPENDENT AND RAS-INDEPENDENT PATHWAYS", EMBO journal, 15(18), 1996, pp. 4940-4948

Abstract

We have investigated the roles of the phosphotyrosine phosphatase Syp(also called SH-PTP2), phospholipase C (PLC) gamma 1, rasGTPase Activating Protein (rasGAP) and the adapter molecules Nck and She in the mitogenic response induced by PDGF in fibroblasts, Two separate approaches were used to inhibit the biological activity of these signalling proteins in vivo. Either glutathione S-transferase (GST) fusion proteinscontaining the SH2 domains of these proteins, or antibodies specific for these polypeptides, were microinjected into cells. GST-SH2 fusion proteins are expected to act as dominant inhibitors by competing for physiological SH2-mediated interactions, while microinjected antibodiescan directly block protein functions, Inhibition of PLC gamma, Syp, She and Nck signals blocked PDGF-stimulated cells in G(1) showing a requirement for these proteins for S-phase entry. Inhibition of rasGAP, in contrast, had no effect on S-phase entry, We next examined which of these signals were required for PDGF-induced cFos expression, a Ras-dependent event important for signalling, By using the same approaches with cells expressing beta-galactosidase under the control of a c-fos promoter, we showed that PLC gamma Syp and She were necessary for ligand-induced cFos expression whereas Nck and phosphatidylinositol 3-kinase were not. From these results we concluded that PDGF generates Ras-dependent and Ras-independent pathways important for DNA synthesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 13:04:20