c-Abl is an effector of Src for growth factor-induced c-myc expression and DNA synthesis

Olivia Furstoss, Karel Dorey, Valérie Simon, Daniela Barilà, Giulio Superti-Furga, Serge Roche

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanism by which the ubiquitously expressed Src family kinases regulate mitogenesis is not well understood. Here we report that cytoplasmic tyrosine kinase c-Abl is an important effector of c-Src for PDGF- and serum-induced DNA synthesis. Inactivation of cytoplasmic c-Abl by the kinase-inactive Abl-PP-K- (AblP242E/P249E/K290M) or by microinjection of Abl neutralizing antibodies inhibited mitogenesis. The kinase-inactive SrcK295M induced a G1 block that was overcome by the constitutively active Abl-PP (AblP242E/P249E). Conversely, the inhibitory effect of Abl-PP-K- was not compensated by Src. c-Src-induced c-Abl activation involves phosphorylation of Y245 and Y412, two residues required for c-Abl mitogenic function. Finally, we found that p53 inactivation and c-myc expression, two cell cycle events regulated by Src during mitogenesis, also implied c-Abl: c-Abl function was dispensable in cells deficient in active p53 and inhibition of c-Abl reduced mitogen-induced c-myc expression. These data identify a novel function of cytoplasmic c-Abl in the signalling pathways regulating growth factor-induced c-myc expression and we propose the existence of a tyrosine kinase signalling cascade (PDGFR/c-Src/c-Abl) important for mitogenesis.

Original languageEnglish
Pages (from-to)514-524
Number of pages11
JournalEMBO Journal
Volume21
Issue number4
DOIs
Publication statusPublished - Feb 15 2002

Keywords

  • c-Abl
  • c-Myc
  • c-Src
  • DNA synthesis
  • Growth factors

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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