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The adaptor protein Tom1L1 is a negative regulator of Src mitogenic signaling induced by growth factors

Mélanie Franco1, Olivia Furstoss, Valérie Simon

  • 1CRBM, CNRS FRE2593, 1919 Route de Mende, 34293 Montpellier Cedex 05, France. Serge.Roche@crbm.cnrs.fr.

Molecular and Cellular Biology
|February 16, 2006
PubMed

Insights

Tom1L1, a novel substrate of Src family kinases (SFK), negatively regulates growth factor-induced DNA synthesis by modulating SFK-receptor association, revealing a new regulatory mechanism for mitogenic signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Src family kinases (SFK) are crucial for growth factor-induced mitogenesis and morphological changes.
  • The specific substrates and regulatory mechanisms of SFK in these processes are not fully understood.

Purpose of the Study:

  • To identify novel substrates and regulators of SFK.
  • To elucidate the role of the identified protein, Tom1L1, in SFK-mediated mitogenic signaling.

Main Methods:

  • Screening of a tyrosine-phosphorylated cDNA expression library using an antiphosphotyrosine antibody.
  • Assessing DNA synthesis and SFK-receptor association in response to growth factors (PDGF) and genetic manipulations.

Main Results:

  • Tom1L1 was identified as a novel substrate and activator of SFK.
  • Tom1L1 inhibits PDGF-induced DNA synthesis by reducing Src association with the receptor.
  • This inhibition can be overcome by c-myc expression or p53 inactivation.
  • Tom1L1 does not affect DNA synthesis induced by a constitutively active Src allele or SFK-regulated actin assembly.

Conclusions:

  • Tom1L1 acts as a negative regulator of SFK mitogenic signaling, independent of its role as a substrate.
  • Tom1L1 modulates SFK-receptor association, defining a novel mechanism for regulating growth factor-induced mitogenesis.
  • Members of the Tom1 family may exhibit functional redundancy in regulating SFK signaling.

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