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Dok-1 independently attenuates Ras/mitogen-activated protein kinase and Src/c-myc pathways to inhibit

Mingming Zhao1, Justyna A Janas, Masaru Niki

  • 1Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.

Molecular and Cellular Biology
|March 16, 2006
PubMed

Insights

Dok-1 adaptor protein inhibits cell growth by disrupting platelet-derived growth factor (PDGF) signaling. It interferes with c-myc induction and Ras/MAPK activation, revealing its tumor suppressor role.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • Dok adaptor proteins regulate kinase signaling.
  • Dok-1 negatively controls cell proliferation induced by growth factors like PDGF.
  • The precise mechanism of Dok-1's inhibitory effect on mitogenesis was unclear.

Purpose of the Study:

  • To elucidate the mechanism by which Dok-1 inhibits growth factor-induced mitogenesis.
  • To investigate Dok-1's role in PDGF-stimulated signaling pathways.

Main Methods:

  • Utilized Dok-1 knockout cells and Dok-1 mutants.
  • Analyzed Dok-1's interaction with specific binding proteins.
  • Investigated PDGF-stimulated c-myc induction and Ras/MAPK activation.

Main Results:

  • Dok-1 hinders PDGF-induced c-myc induction by recruiting Csk to Src kinases.
  • Dok-1 attenuates PDGF-induced MAPK activation via Ras-GAP and other interacting proteins.
  • Both pathways contribute to Dok-1's overall inhibitory effect on mitogenesis.

Conclusions:

  • Dok-1 inhibits growth factor-induced mitogenesis by tethering signaling components to the cell membrane.
  • Dok-1's regulation of c-myc and MAPK pathways provides a mechanistic basis for its tumor suppressor function.

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