RGD Reference Report - AS160 phosphotyrosine-binding domain constructs inhibit insulin-stimulated GLUT4 vesicle fusion with the plasma membrane. - Rat Genome Database
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AS160 phosphotyrosine-binding domain constructs inhibit insulin-stimulated GLUT4 vesicle fusion with the plasma membrane.

Authors: Koumanov, F  Richardson, JD  Murrow, BA  Holman, GD 
Citation: Koumanov F, etal., J Biol Chem. 2011 May 13;286(19):16574-82. doi: 10.1074/jbc.M111.226092. Epub 2011 Mar 17.
RGD ID: 7247577
Pubmed: (View Article at PubMed) PMID:21454690
DOI: Full-text: DOI:10.1074/jbc.M111.226092

AS160 (TBC1D4) is a known Akt substrate that is phosphorylated downstream of insulin action and that leads to regulated traffic of GLUT4. As GLUT4 vesicle fusion with the plasma membrane is a highly regulated step in GLUT4 traffic, we investigated whether AS160 and 14-3-3 interactions are involved in this process. Fusion was inhibited by a human truncated AS160 variant that encompasses the first N-terminal phosphotyrosine-binding (PTB) domain, by either of the two N-terminal PTB domains, and by a tandem construct of both PTB domains of rat AS160. We also found that in vitro GLUT4 vesicle fusion was strongly inhibited by the 14-3-3-quenching inhibitors R18 and fusicoccin. To investigate the mode of interaction of AS160 and 14-3-3, we examined insulin-dependent increases in the levels of these proteins on GLUT4 vesicles. 14-3-3gamma was enriched on insulin-stimulated vesicles, and its binding to AS160 on GLUT4 vesicles was inhibited by the AS160 tandem PTB domain construct. These data suggest a model for PTB domain action on GLUT4 vesicle fusion in which these constructs inhibit insulin-stimulated 14-3-3gamma interaction with AS160 rather than AS160 phosphorylation.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component
vesicle  (IDA)

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Tbc1d4  (TBC1 domain family, member 4)
Ywhab  (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta)
Ywhag  (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma)


Additional Information