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 journalArticle

99 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)268-274
Number of pages7
JournalNature Cell Biology
Volume6
Issue number3
Publication statusPublished - Mar 2004

Fingerprint

Guanine Nucleotide Exchange Factors
Receptor Protein-Tyrosine Kinases
Tyrosine
Intercellular Signaling Peptides and Proteins
Phosphorylation
Oncogene Proteins
Actin Cytoskeleton
Protein-Tyrosine Kinases
Actins
Signal Transduction
Phosphotransferases
Pharmacology
In Vitro Techniques

ASJC Scopus subject areas

  • Cell Biology

Cite this

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.

In: Nature Cell Biology, Vol. 6, No. 3, 03.2004, p. 268-274.

Research output: Contribution to journalArticle

Sini, Patrizia ; Cannas, Angela ; Koleske, Anthony J. ; Di Fiore, Pier Paolo ; Scita, Giorgio. / Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation. In: Nature Cell Biology. 2004 ; Vol. 6, No. 3. pp. 268-274.
@article{37fd62b652bc4708a72a12cb6560b627,
title = "Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation",
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.",
author = "Patrizia Sini and Angela Cannas and Koleske, {Anthony J.} and {Di Fiore}, {Pier Paolo} and Giorgio Scita",
year = "2004",
month = "3",
language = "English",
volume = "6",
pages = "268--274",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Abl-dependent tyrosine phosphorylation of Sos-1 mediates growth-factor-induced Rac activation

AU - Sini, Patrizia

AU - Cannas, Angela

AU - Koleske, Anthony J.

AU - Di Fiore, Pier Paolo

AU - Scita, Giorgio

PY - 2004/3

Y1 - 2004/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=1542609420&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542609420&partnerID=8YFLogxK

M3 - Article

C2 - 15039778

AN - SCOPUS:1542609420

VL - 6

SP - 268

EP - 274

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 3

ER -