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.
Xie
Xiangyang
X
National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Chen
Yu
Y
Xue
Peng
P
Fan
Yong
Y
Deng
Yongqiang
Y
Peng
Gong
G
Yang
Fuquan
F
Xu
Tao
T
D041721:3T3-L1 Cells; D000074183:ATPases Associated with Diverse Cellular Activities; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D003600:Cytosol / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005947:Glucose / Q000493:pharmacokinetics; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering
D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D034741:RNA, Small Interfering; C495693:Slc2a4 protein, mouse; C505647:Tbc1d4 protein, mouse; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human; C518330:RUVBL2 protein, mouse; D005947:Glucose