The non-receptor tyrosine kinase Abl participates in receptor tyrosine kinase (RTK)-induced actin cytoskeleton remodelling, a signalling pathway in which the function of Rac is pivotal. More importantly, the activity of Rac is indispensable for the leukaemogenic ability of the BCR-Abl oncoprotein. Thus, Rac might function downstream of Abl and be activated by it. Here, we elucidate the molecular mechanisms through which Abl signals to Rac in RTK-activated pathways. We show that Sos-1, a dual guanine nucleotide-exchange factor (GEF), is phosphorylated on tyrosine, after activation of RTKs, in an Abl-dependent manner. Sos-1 and Abl interact in vivo, and Abl-induced tyrosine phosphorylation of Sos-1 is sufficient to elicit its Rac-GEF activity in vitro. Genetic or pharmacological interference with Abl (and the related kinase Arg) resulted in a marked decrease in Rac activation induced by physiological doses of growth factors. Thus, our data identify the molecular connections of a pathway RTKs-Abl-Sos-1-Rac that is involved in signal transduction and actin remodelling.
Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation / P. Sini, A. Cannas, A. J. Koleske, P. P. Di Fiore, G. Scita. - In: NATURE CELL BIOLOGY. - ISSN 1465-7392. - 6:3(2004 Mar), pp. 268-274.
Titolo: | Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation |
Autori: | DI FIORE, PIER PAOLO (Penultimo) SCITA, GIORGIO (Ultimo) |
Parole Chiave: | C-ABL; kinase-activity; factor receptor; transforming activity; actin cytoskeleton; rho-GTpases; SH3 domain; protein; exchange; EPS8 |
Settore Scientifico Disciplinare: | Settore MED/04 - Patologia Generale |
Data di pubblicazione: | mar-2004 |
Rivista: | |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/ncb1096 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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