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.