beta-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), alpha-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, alpha-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 beta-arrestin 1 in the regulation of alpha-thrombin-induced Akt activity. In addition to their importance in receptor down-regulation, beta-arrestins are now known to scaffold proteins involved in stimulating specific signaling pathways. My preliminary data show that equal to or precedes -thrombin activates a rapid Akt activity in a beta-arrestin 1-dependent manner in IIC9 cells.
Goel
Reema
R
Department of Pharmacological and Physiological Sciences, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Baldassare
Joseph J
JJ
D000818:Animals; D019390:Arrestins / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013917:Thrombin / Q000502:physiology*; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
C000605253:ARRB1 protein, human; D019390:Arrestins; D011518:Proto-Oncogene Proteins; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D011505:Protein-Tyrosine Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D013917:Thrombin