RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation.

In fat and muscle cells, insulin-stimulated glucose uptake is mainly mediated by glucose transporter 4 (GLUT4), which translocates from intracellular compartments to the cell surface in response to insulin stimulation. AS160 is one of the substrates of Akt and plays important roles in insulin-regulated GLUT4 translocation. In this study, RuvB-like protein 2 (RUVBL2) is identified as a new AS160-binding protein using mammalian tandem affinity purification (TAP) combined with mass spectrometry. In 3T3-L1 adipocytes, RUVBL2 is highly expressed and is mainly distributed in the cytosol. Depletion of RUVBL2 in adipocytes inhibits insulin-stimulated GLUT4 translocation and glucose uptake through reducing insulin-stimulated AS160 phosphorylation. However, introduction of human RUVBL2 can reverse this inhibitory effect. These data suggest that RUVBL2 plays an important role in insulin-stimulated GLUT4 translocation through its interaction with AS160.