The proto-oncogene c-Cbl is a negative regulator of DNA synthesis initiated by both receptor and cytoplasmic tyrosine kinases

Martin A. Broome, Maria L. Galisteo, Joseph Schlessinger, Sara A. Courtneidge

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

In C. elegans, genetic and biochemical data indicate that the Cbl homolog Sli-1 attenuates Let-23 (EGFR) signaling. To investigate whether c-Cbl might have a role in mammalian growth factor-mediated mitogenic signaling, we microinjected NIH3T3 mouse fibroblasts with expression plasmids encoding wt and G306ECbl (a 'loss of function' mutant identified in C. elegans). We observed inhibition of PDGF BB- and EGF-induced DNA synthesis by wt Cbl but not the mutant. Microinjection of two different affinity purified polyclonal antisera against Cbl boosted a suboptimal PDGF-stimulated mitogenic response. The inhibition of both PDGF BB- and EGF-induced DNA synthesis by wt Cbl was reversed by co-expression with Myc but not with Fos. DNA synthesis initiated by constitutively activated Src was also blocked by Cbl expression, but curiously by the G306E mutant as well. These data are all consistent with the proposition that Cbl negatively affects mitogenic signaling in mammalian fibroblasts.

Original languageEnglish (US)
Pages (from-to)2908-2912
Number of pages5
JournalOncogene
Volume18
Issue number18
DOIs
StatePublished - May 6 1999

Keywords

  • Growth-factor-signaling
  • Mitogenesis
  • Src
  • c-Cbl

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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