A novel role for Gqα in α-thrombin-mediated mitogenic signalling pathways

Alice Gardner, Polly J. Phillips-Mason, Daniel M. Raben, Joseph J. Baldassare

Research output: Contribution to journalArticlepeer-review

Abstract

α-Thrombin activates several G-proteins including members of the Gq, Gi, and G12/13 families, although the physiological importance of these proteins is still not completely understood. We specifically investigated the role of Gqα in modulating α-thrombin-induced mitogenesis. In Gqa1 cells, a stable cell line expressing reduced amounts of Gqα, concentrations of α-thrombin (1 NIH unit/ml), which induce cell cycle reentry and progression into S phase in wild-type IIC9 cells, do not stimulate phosphatidylinositol (PI) hydrolysis, the rapid early phase of ERK activity, and transit through G1 into S phase as quantified by cyclin-dependent kinase (CDK)4-cyclin D activity and [3H]thymidine incorporation. Interestingly, high concentrations of α-thrombin restore these activities and cell cycle progression into S phase. While, it is well documented that α-thrombin-induced sustained ERK activity mediates important responses for transit through G1 into S phase, the importance of the rapid, Gq-dependent phase as a prerequisite for α-thrombin-mediated mitogenesis has not been appreciated.

Original languageEnglish (US)
Pages (from-to)499-507
Number of pages9
JournalCellular Signalling
Volume14
Issue number6
DOIs
StatePublished - Mar 26 2002

Keywords

  • CDK, Cyclin-dependent kinase
  • ERK, Extracellular-regulated kinase
  • GPCRs, G-protein-coupled receptors
  • PAR, Protease-activated receptor

ASJC Scopus subject areas

  • Cell Biology

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