Ash/Grb-2, a SH2/SH3-containing protein, couples to signaling for mitogenesis and cytoskeletal reorganization by EGF and PDGF.
EMBO J
; 12(9): 3467-73, 1993 Sep.
Article
em En
| MEDLINE
| ID: mdl-8253073
ABSTRACT
The Src homology (SH) region 2 binds to phosphorylated tyrosine residues and SH3 domains may interact with cytoskeletal molecules and GTPase-activating proteins for Rho/Rac proteins (the small GTP-binding proteins related to Ras). The recently cloned Ash/Grb-2 protein, a 25-28 kDa molecule composed entirely of SH2 and SH3 domains, is a mammalian homolog of the Caenorhabditis elegans Sem-5 protein, which communicates between a receptor protein tyrosine kinase and a Ras protein. In the present study the function of Ash/Grb-2 was investigated by microinjecting cells with an anti-Ash antibody. The antibody abolished both S phase entry and the reorganization of actin assembly to ruffle formation upon stimulation with epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). On the other hand, anti-Ash antibody had no effect on S phase entry or actin stress fiber formation induced by either serum or lysophosphatidic acid. Since the induction of DNA synthesis, ruffle induction and stress fiber formation involve a function of Ras, Rac activation and Rho activation respectively, the findings strongly suggest that Ash plays a critical role in the signaling of both pathways downstream from growth factor receptors to Ras and Rac. Consistent with this, Ash co-precipitated with EGF receptor from EGF-stimulated cells. Other proteins of approximately 21, 29, 135 and 160 kDa were also detected in the anti-Ash antibody immunoprecipitates, suggesting a role of Ash as a linker molecule in signal transduction downstream of growth factor receptors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto
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Fator de Crescimento Derivado de Plaquetas
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Transdução de Sinais
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Proteínas
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Divisão Celular
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Proteínas de Ligação ao GTP
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Proteínas Adaptadoras de Transdução de Sinal
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Fator de Crescimento Epidérmico
Limite:
Animals
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Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
1993
Tipo de documento:
Article
País de afiliação:
Japão