TY - JOUR
T1 - A novel role for Gqα in α-thrombin-mediated mitogenic signalling pathways
AU - Gardner, Alice
AU - Phillips-Mason, Polly J.
AU - Raben, Daniel M.
AU - Baldassare, Joseph J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - CDK, Cyclin-dependent kinase
KW - ERK, Extracellular-regulated kinase
KW - GPCRs, G-protein-coupled receptors
KW - PAR, Protease-activated receptor
UR - http://www.scopus.com/inward/record.url?scp=0036118290&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036118290&partnerID=8YFLogxK
U2 - 10.1016/S0898-6568(01)00279-0
DO - 10.1016/S0898-6568(01)00279-0
M3 - Article
C2 - 11897490
AN - SCOPUS:0036118290
SN - 0898-6568
VL - 14
SP - 499
EP - 507
JO - Cellular Signalling
JF - Cellular Signalling
IS - 6
ER -