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Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation

Sini, Patrizia, Cannas, Angela, Koleske, Anthony J., Di Fiore, Pier Paolo, Scita, Giorgio·2004·Nature Cell Biology
DOI 10.1038/ncb1096
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Abstract

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.

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Metadata

Authors
Sini, P., Cannas, A., Koleske, A. J., Di Fiore, P. P., & Scita, G.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2004-02-22
Volume
6
Issue
3
Pages
268-274
ISSN
  • 1465-7392
  • 1476-4679
DOI
10.1038/ncb1096
Cited by
130
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation. https://app.cochat.ai/papers/10.1038/ncb1096
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Sini, P., Cannas, A., Koleske, A. J., Di Fiore, P. P., & Scita, G. (2004). Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation. Nature Cell Biology. https://doi.org/10.1038/ncb1096