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Divergent roles of c-Src in controlling platelet-derived growth factor-dependent signaling in fibroblasts

Kavita Shah1, Fabien Vincent

  • 1Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. shah23@purdue.edu

Molecular Biology of the Cell
|September 2, 2005
PubMed

Insights

This study used a chemical-genetic approach to investigate c-Src

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Cancer research

Background:

  • Platelet-derived growth factor (PDGF) signaling is complex.
  • The exact roles of Src family kinases in PDGF signaling remain unclear.
  • Lack of specific temporal control hinders investigation.

Purpose of the Study:

  • To elucidate the cellular functions of c-Src in PDGF signaling.
  • To identify novel c-Src phosphorylation targets.
  • To define c-Src's influence on transcriptional regulation.

Main Methods:

  • Chemical-genetic approach for c-Src manipulation.
  • Global substrate labeling for phosphoproteomics.
  • Transcriptional analysis to assess gene expression changes.

Main Results:

  • c-Src significantly controls actin reorganization and chemotaxis.
  • Multiple cytoskeletal proteins and chemotaxis genes are regulated by c-Src.
  • c-Src transmits conflicting signals via PI3K and Ras pathways impacting DNA synthesis.

Conclusions:

  • c-Src plays a critical role in PDGF-mediated actin dynamics and cell migration.
  • c-Src influences gene expression related to chemotaxis.
  • Src family kinases regulate PDGF responses at both transcriptional and translational levels.

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