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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Cyclin E and cyclin A are likely targets of Src for PDGF-induced DNA synthesis in fibroblasts

Olivia Furstoss1, Gaël Manes, Serge Roche

  • 1CRBM, CNRS UPR-1086, 1919 route de Mende, 34293 Montpellier, France.

FEBS Letters
|September 5, 2002
PubMed

Insights

Adenovirus E1A protein overrides Src kinase-induced cell cycle arrest by upregulating cyclins E and A. This suggests Src family kinases target these cyclins to regulate platelet-derived growth factor (PDGF)-induced DNA synthesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Virology

Background:

  • The regulation of DNA synthesis by Src family tyrosine kinases in response to platelet-derived growth factor (PDGF) is not fully understood.
  • Understanding these pathways is crucial for comprehending cell proliferation and potential therapeutic interventions.

Purpose of the Study:

  • To elucidate the mechanism by which Src family kinases regulate PDGF-induced DNA synthesis.
  • To investigate the role of adenovirus E1A in overriding cell cycle arrest mediated by kinase-inactive Src.

Main Methods:

  • Utilized adenovirus E1A and a kinase-inactive Src mutant (SrcK(-)) in fibroblast cell models.
  • Assessed the impact on cell cycle progression, specifically the G1 block.
  • Analyzed the expression levels of cyclins E, A, and D1, and the activity of the pocket protein pRb.

Main Results:

  • Adenovirus E1A protein successfully overrides the G1 cell cycle block induced by SrcK(-).
  • E1A upregulates cyclin E and cyclin A expression and inactivates pRb, independent of pRb itself.
  • SrcK(-) inhibits PDGF-induced expression of cyclins E and A, an effect reversed by E1A.
  • Constitutive expression of cyclins E and A, but not D1, restored mitogenesis inhibited by SrcK(-).

Conclusions:

  • Cyclin E and cyclin A are identified as key targets of Src family kinases in mediating PDGF-induced DNA synthesis.
  • Adenovirus E1A acts by modulating these cyclin pathways to promote cell proliferation.

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