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Titolo:
Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo)
Autore:
Bouscary, D; Lecoq-Lafon, C; Chretien, S; Zompi, S; Fichelson, S; Muller, O; Porteu, F; Dusanter-Fourt, I; Gisselbrecht, S; Mayeux, P; Lacombe, C;
Indirizzi:
Univ Paris 05, Hop Cochin, ICGM, INSERM,U363, F-75014 Paris, France Univ Paris 05 Paris France F-75014 M, INSERM,U363, F-75014 Paris, France AP HP, Hop Cochin, Serv Hematol, Paris, France AP HP Paris FranceAP HP, Hop Cochin, Serv Hematol, Paris, France Hop Cochin, Lab Rech Hemobiol, F-75014 Paris, France Hop Cochin Paris France F-75014 Lab Rech Hemobiol, F-75014 Paris, France
Titolo Testata:
ONCOGENE
fascicolo: 18, volume: 20, anno: 2001,
pagine: 2197 - 2204
SICI:
0950-9232(20010426)20:18<2197:ROGPIP>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
C-MPL LIGAND; PLECKSTRIN HOMOLOGY DOMAIN; GROWTH-FACTOR RECEPTOR; INDUCED MEGAKARYOCYTIC DIFFERENTIATION; PHOSPHOTYROSINE-BINDING DOMAIN; TYROSINE PHOSPHORYLATION; CYTOPLASMIC DOMAIN; INSULIN-RECEPTOR; EPITHELIAL MORPHOGENESIS; SHC PHOSPHORYLATION;
Keywords:
Gab proteins; phosphatidylinositol 3-kinase; Akt; thrombopoietin; cytokines; signal transduction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Lacombe, C Univ Paris 05, Hop Cochin, ICGM, INSERM,U363, 27 Rue Faubourg St Jacques, F-75014 Paris, France Univ Paris 05 27 Rue Faubourg St Jacques Paris France F-75014
Citazione:
D. Bouscary et al., "Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo)", ONCOGENE, 20(18), 2001, pp. 2197-2204

Abstract

In this study, we show that upon thrombopoietin (Tpo) stimulation the two adapter proteins Gab1 and Gab2 are strongly tyrosine phosphorylated and associated with Shc, SHP2, PI 3-kinase and Grb2 in mpl-expressing UT7 cells. Although Gab1 and Gab2 seem to mediate overlapping biological signals in many cells, only Gab1 is expressed and phosphorylated in response to Tpo in primary human megakaryocytic progenitors; furthermore, it associates with thesame proteins. Although a Low level of tyrosine phosphorylated IRS-2 protein is also detected in PI 3-kinase immunoprecipitates, cab proteins are theessential proteins associated with PI 3-kinase after Tpo stimulation. We demonstrate that, albeit no association is detected between the Tpo receptormpl and Gab proteins, Y112 located in the C-terminal cytoplasmic domain ofmpl is required for Gab1/2 tyrosine phosphorylation, Gab proteins are not tyrosine phosphorylated after Tpo stimulation of UT-7 and Ba/F3 cells expressing a mpl mutant lacking Y112. Moreover, no activation of the PI 3-kinase/Akt pathway is observed in cells expressing this mpl mutant. Finally, we show that this mutant does not allow cell proliferation, thereby confirming that PI 3-kinase activation is required for Tpo-induced cell proliferation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 22:13:43