Title

C2 Domain-Containing Phosphoprotein Cdp138 Regulates Glut4 Insertion Into The Plasma Membrane

Abstract

The protein kinase B β (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 Ca 2+ and lipid membranes. CDP138 mutants lacking the Ca 2+-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. © 2011 Elsevier Inc.

Publication Date

9-7-2011

Publication Title

Cell Metabolism

Volume

14

Issue

3

Number of Pages

378-389

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.cmet.2011.06.015

Socpus ID

80052770295 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/80052770295

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