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Cell cycle-dependent activation of Ras

S J Taylor1, D Shalloway

  • 1Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853, USA.

Current Biology : CB
|December 1, 1996
PubMed
Summary
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Ras protein activation occurs during the G1 phase of the cell cycle, independent of growth factor signaling. This suggests a novel intrinsic regulation mechanism and alternative Ras effector pathways during cell cycle progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Ras proteins are crucial for signal transduction from cell-surface receptors to the nucleus, influencing cellular proliferation and differentiation.
  • Ras is well-established to mediate mitogenic signals from growth factors, facilitating cell-cycle entry.
  • The precise role of Ras in controlling signaling events during cell-cycle progression and its activation timing remain unclear.

Purpose of the Study:

  • To investigate whether Ras controls signaling events during cell-cycle progression.
  • To determine the specific point in the cell cycle at which Ras is activated.

Main Methods:

  • Development of a novel, functional assay for detecting cellular activated Ras.
  • Analysis of Ras activation in HeLa cells and NIH 3T3 fibroblasts at different cell-cycle stages.

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Main Results:

  • Ras activation was detected in HeLa cells post-mitosis and in NIH 3T3 fibroblasts after serum stimulation.
  • Peak Ras activation occurred in mid-G1 phase in both cell types.
  • Ras activation in mid-G1 phase was RNA and protein synthesis-dependent and not linked to Shc protein tyrosine phosphorylation or Grb2 binding.
  • Ras activation and extracellular-signal regulated kinase (ERK) activation were not temporally correlated during G1 progression.

Conclusions:

  • Ras activation during mid-G1 phase appears to involve a novel regulatory mechanism intrinsic to cell-cycle progression, distinct from rapid growth factor-induced activation.
  • The temporal uncoupling of Ras and ERK activation suggests that Ras may engage alternative effector pathways during G1 phase.