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

Patrizia Sini, Angela Cannas, Anthony J. Koleske, Pier Paolo Di Fiore, Giorgio Scita

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)268-274
Number of pages7
JournalNature Cell Biology
Issue number3
Publication statusPublished - Mar 2004

ASJC Scopus subject areas

  • Cell Biology


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