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Titolo:
Identification of epidermal growth factor receptor-Grb2-associated Binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression
Autore:
Kameda, H; Risinger, JI; Han, BB; Baek, SJ; Barrett, JC; Glasglow, WC; Eling, TE;
Indirizzi:
NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA NIEHS Res Triangle Pk NC USA 27709 ab, NIH, Res Triangle Pk, NC 27709 USA Mercer Univ, Sch Med, Div Basic Med Sci, Macon, GA 31207 USA Mercer Univ Macon GA USA 31207 ed, Div Basic Med Sci, Macon, GA 31207 USA
Titolo Testata:
CELL GROWTH & DIFFERENTIATION
fascicolo: 6, volume: 12, anno: 2001,
pagine: 307 - 318
SICI:
1044-9523(200106)12:6<307:IOEGFR>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-TYROSINE-PHOSPHATASE; TUMOR-SUPPRESSOR GENE; SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; INSULIN-RECEPTOR SUBSTRATE-1; PLECKSTRIN HOMOLOGY DOMAIN; LINOLEIC-ACID METABOLITE; PHOSPHOLIPASE C-GAMMA; HAMSTER EMBRYO CELLS; GRB2 BINDING-SITE; DOCKING PROTEIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
76
Recensione:
Indirizzi per estratti:
Indirizzo: Eling, TE NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA NIEHS POB 12233 Res Triangle Pk NC USA 27709 le Pk, NC 27709 USA
Citazione:
H. Kameda et al., "Identification of epidermal growth factor receptor-Grb2-associated Binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression", CELL GROWTH, 12(6), 2001, pp. 307-318

Abstract

The adaptor protein Grb2-associated binder-1 (Gab1) is known to bind to the SHP-2 tyrosine phosphatase on epidermal growth factor (EGF) receptor stimulation, To clarify the roles of these two proteins in EGF receptor (EGFR) signaling and determine their possible alteration during neoplastic cell progression, we studied these proteins in a Syrian hamster embryo (SHE) cell line model of neoplastic progression. Specifically, we used ashestos-transformed SHE fibroblasts: the 10W+8 clone, which is immortal but nontumorigenic; and the 10W2T clone, which is tumorigenic. Gab1 was detected, and the EGF-dependent formation of the EGFR-Gab1-SHP-2 complex was observed in 10W+8 cells. After cloning hamster Gab1 cDNA, exogenous expression of Gab1 significantly enhanced EGF-dependent mitogenic activity in 10W+8 cells, On the other hand, Gab1 was not detected in 10W2T cells, and the EGF-dependent association of SHP-2 with EGFR was also absent. Exogenous Gab1 expression in transfected 10W2T cells restored the EGF-dependent association of SHP-2 with EGFR, although it only showed a marginal effect on EGF-dependent mitogenic activity. Thus, Gab1 plays a pivotal role in the EGFR signaling pathway via the formation of the EGFR-Gab1-SHP-2 complex, and alteration in the expression and function of Gab1 is implicated in the neoplastic progression of SHEcells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 08:26:07