The TC10-interacting protein CIP4/2 is required for insulin-stimulated Glut4 translocation in 3T3L1 adipocytes.
The GTPase TC10 plays a critical role in insulin-stimulated glucose transport. We report here the identification of the TC10-interacting protein CIP4/2 (Cdc42-interacting protein 4/2) as an effector in this pathway. CIP4/2 localizes to an intracellular compartment under basal conditions and translocates to the plasma membrane on insulin stimulation. Overexpression of constitutively active TC10 brings CIP4/2 to the plasma membrane, whereas overexpression of an inhibitory form of TC10 blocks the translocation of CIP4/2 produced by insulin. Overexpression of mutant forms of CIP4/2 containing an N-terminal deletion or with diminished TC10 binding inhibits insulin-stimulated Glut4 translocation. These data suggest that CIP4/2 may play an important role in insulin-stimulated glucose transport as a downstream effector of TC10.
Chang
Louise
L
Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Adams
Rachael D
RD
Saltiel
Alan R
AR
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D017353:Gene Deletion; D051275:Glucose Transporter Type 4; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D018909:src Homology Domains
D018076:DNA, Complementary; D051275:Glucose Transporter Type 4; D007328:Insulin; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; C495693:Slc2a4 protein, mouse; C485787:Trip10 protein, mouse; D005982:Glutathione Transferase; C503260:Rhoq protein, mouse; D020741:rho GTP-Binding Proteins