The association of ClipR-59 protein with AS160 modulates AS160 protein phosphorylation and adipocyte Glut4 protein membrane translocation.
ClipR-59 is a membrane-associated protein and has been implicated in membrane signaling and vesicle trafficking. Recently, we have identified ClipR-59 as an Akt-interacting protein, and we have found that, by interacting with Akt, ClipR-59 modulates Akt subcellular compartmentalization and Akt substrate AS160 phosphorylation, thereby promoting Glut4 membrane translocation. Here, we have further investigated the regulatory effects of ClipR-59 on AS160 phosphorylation and subsequent adipocyte glucose transport. Our data showed that ClipR-59 interacted with AS160, which was mediated by the ankyrin repeats of ClipR-59 and regulated by insulin signaling. Moreover, the data also demonstrated that the interaction of ClipR-59 with AS160 was required for ClipR-59 to modulate Glut4 membrane translocation as ΔANK-ClipR-59, an AS160 interaction-defective mutant, failed to promote AS160 phosphorylation, Glut4 membrane translocation, and glucose transport induced by insulin in 3T3-L1 adipocytes. Because ClipR-59 also interacts with Akt and enhances the interaction between Akt and AS160, we suggest that ClipR-59 functions as a scaffold protein to facilitate Akt-mediated AS160 phosphorylation, thereby regulating glucose transport.
Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA.
Wenying
W
Ren
Sarwat
S
Cheema
Keyong
K
Du
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D015398:Signal Transduction; D015854:Up-Regulation
C539981:ClipR-59 protein, mouse; D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D008869:Microtubule-Associated Proteins; C505647:Tbc1d4 protein, mouse