AS160 is a Rab GTPase-activating protein (GAP) that is part of a subfamily of Rab GAPs that contain a conserved TBC1 (Tre-2/Bub2/Cdc16) domain (1). It is a negative regulator of GLUT4 vesicle translocation to the plasma membrane. The phosphorylation of TBC1D4 suppresses its GAP activity, thereby triggering docking of GLUT4 vesicles (2). AS160 is phosphorylated at multiple sites including Threonine 642. Insulin and IGF-1 induce 14-3-3 binding to AS160 mainly via phospho-Threonine 642 (3).
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