Unknown

Dataset Information

0

The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.


ABSTRACT: The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes. Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect. In the present study we detected several new functional features of AS160. The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila. This region also contains a nonoverlapping intracellular GLUT4-containing storage vesicle (GSV) cargo-binding site. The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation. Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity. We propose a model wherein AS160 acts as a regulatory switch in the docking and/or fusion of GSVs with the PM.

SUBMITTER: Tan SX 

PROVIDER: S-EPMC3510527 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.

Tan Shi-Xiong SX   Ng Yvonne Y   Burchfield James G JG   Ramm Georg G   Lambright David G DG   Stöckli Jacqueline J   James David E DE  

Molecular and cellular biology 20121008 24


The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes. Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect. In the present study we detected several new functional features of AS160. The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other relate  ...[more]

Shared Molecules

Only show the datasets with similarity scores above: 0.5
     

Similar Datasets

| S-EPMC6349102 | biostudies-literature
| S-EPMC1237142 | biostudies-other
| S-EPMC3081066 | biostudies-literature
| S-EPMC3093885 | biostudies-literature
| S-EPMC2781555 | biostudies-literature
| S-EPMC3143591 | biostudies-literature
| S-EPMC9881301 | biostudies-literature
| S-EPMC4086491 | biostudies-literature
| S-EPMC1874243 | biostudies-other
| S-EPMC10435366 | biostudies-literature