C2 Domain-Containing Phosphoprotein CDP138 Regulates GLUT4 Insertion into the Plasma Membrane
Abbreviated Journal Title
PROTEIN-KINASE B; INSULIN SIGNALING PATHWAY; GTPASE-ACTIVATING-PROTEIN; GLUT4-CONTAINING VESICLES; GLUCOSE-TRANSPORTER; 3T3-L1 ADIPOCYTES; TRANSLOCATION; PHOSPHORYLATION; FUSION; AKT2; Cell Biology; Endocrinology & Metabolism
The protein kinase B-beta (Akt2) pathway is known to mediate insulin-stimulated glucose transport through increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane (PM). Combining quantitative phosphoproteomics with RNAi-based functional analyses, we show that a previously uncharacterized 138 kDa C2 domain-containing phosphoprotein (CDP138) is a substrate for Akt2, and is required for optimal insulin-stimulated glucose transport, GLUT4 translocation, and fusion of GLUT4 vesicles with the PM in live adipocytes. The purified C2 domain is capable of binding Ca2+ and lipid membranes. CDP138 mutants lacking the Ca2+-binding sites. in the C2 domain or Akt2 phosphorylation site S197 inhibit insulin-stimulated GLUT4 insertion into the PM, a rate-limiting step of GLUT4 translocation. Interestingly, CDP138 is dynamically associated with the PM and GLUT4-containing vesicles in response to insulin stimulation. Together, these results suggest that CDP138 is a key molecule linking the Akt2 pathway to the regulation of GLUT4 vesicle-PM fusion.
"C2 Domain-Containing Phosphoprotein CDP138 Regulates GLUT4 Insertion into the Plasma Membrane" (2011). Faculty Bibliography 2010s. 2120.