β-arrestin 1 couples thrombin to the rapid activation of the Akt pathway

In a variety of cell types including chinese hamster embryonic fibroblasts (IIC9 cells), α-thrombin is a potent mitogen. Thrombin irreversibly activates Par 1, a member of the seven membrane-spanning superfamily of G protein-coupled receptors (GPCRs). This, in turn, activates several heterotrimeric G proteins and induces signaling pathways that are critical for cell cycle reentry and proliferation. In IIC9 cells, α-thrombin activates the phosphatidylinositol-3-OH kinase (PI 3-Kinase)/Akt pathway, which is essential for G₁ cell cycle progression. At present the mechanism for activation and regulation of the PI 3-kinase/Akt pathway is not fully understood. My preliminary data demonstrates a role for β-arrestin 1 in the regulation of α-thrombin-induced Akt activity. In addition to their importance in receptor down-regulation, β-arrestins are now known to scaffold proteins involved in stimulating specific signaling pathways. My preliminary data show that <-thrombin activates a rapid Akt activity in a β-arrestin 1-dependent manner in IIC9 cells.