A novel role for Gq alpha in alpha-thrombin-mediated mitogenic signalling pathways.
alpha-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 Gq alpha in modulating alpha-thrombin-induced mitogenesis. In Gqa1 cells, a stable cell line expressing reduced amounts of Gq alpha, concentrations of alpha-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 alpha-thrombin restore these activities and cell cycle progression into S phase. While, it is well documented that alpha-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 alpha-thrombin-mediated mitogenesis has not been appreciated.
Gardner
Alice
A
Department of Pharmacological and Physiological Sciences, St. Louis University Medical School, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
Phillips-Mason
Polly J
PJ
Raben
Daniel M
DM
Baldassare
Joseph J
JJ
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology*; D009154:Mutation; D013917:Thrombin / Q000494:pharmacology*
D016373:DNA, Antisense; D007295:Inositol Phosphates; D008934:Mitogens; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins