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dc.contributor.authorJiang, Zhen Y.
dc.contributor.authorChawla, Anil
dc.contributor.authorBose, Avirup
dc.contributor.authorWay, Michael
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:10:03.000
dc.date.accessioned2022-08-23T16:53:54Z
dc.date.available2022-08-23T16:53:54Z
dc.date.issued2001-11-06
dc.date.submitted2008-08-04
dc.identifier.citationJ Biol Chem. 2002 Jan 4;277(1):509-15. Epub 2001 Nov 1. <a href="http://dx.doi.org/10.1074/jbc.M108280200">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.M108280200
dc.identifier.pmid11694514
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42378
dc.description.abstractRecruitment of intracellular glucose transporter 4 (GLUT4) to the plasma membrane of fat and muscle cells in response to insulin requires phosphatidylinositol (PI) 3-kinase as well as a proposed PI 3-kinase-independent pathway leading to activation of the small GTPase TC10. Here we show that in cultured adipocytes insulin causes acute cortical localization of the actin-regulatory neural Wiskott-Aldrich syndrome protein (N-WASP) and actin-related protein-3 (Arp3) as well as cortical F-actin polymerization by a mechanism that is insensitive to the PI 3-kinase inhibitor wortmannin. Expression of the dominant inhibitory N-WASP-DeltaWA protein lacking the Arp and actin binding regions attenuates the cortical F-actin rearrangements by insulin in these cells. Remarkably, the N-WASP-DeltaWA protein also inhibits insulin action on GLUT4 translocation, indicating dependence of GLUT4 recycling on N-WASP-directed cortical F-actin assembly. TC10 exhibits sequence similarity to Cdc42 and has been reported to bind N-WASP. We show the inhibitory TC10 (T31N) mutant, which abrogates insulin-stimulated GLUT4 translocation and glucose transport, also inhibits both cortical localization of N-WASP and F-actin formation in response to insulin. These findings reveal that N-WASP likely functions downstream of TC10 in a PI 3-kinase-independent insulin signaling pathway to mobilize cortical F-actin, which in turn promotes GLUT4 responsiveness to insulin.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11694514&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M108280200
dc.subject1-Phosphatidylinositol 3-Kinase
dc.subjectActin-Related Protein 2
dc.subjectActin-Related Protein 3
dc.subjectActins
dc.subjectBiological Transport
dc.subject*Cytoskeletal Proteins
dc.subjectGlucose Transporter Type 4
dc.subjectHumans
dc.subjectInsulin
dc.subjectMonosaccharide Transport Proteins
dc.subject*Muscle Proteins
dc.subjectNerve Tissue Proteins
dc.subjectWiskott-Aldrich Syndrome Protein, Neuronal
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleA phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose transporter recycling
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume277
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/732
dc.identifier.contextkey564647
html.description.abstract<p>Recruitment of intracellular glucose transporter 4 (GLUT4) to the plasma membrane of fat and muscle cells in response to insulin requires phosphatidylinositol (PI) 3-kinase as well as a proposed PI 3-kinase-independent pathway leading to activation of the small GTPase TC10. Here we show that in cultured adipocytes insulin causes acute cortical localization of the actin-regulatory neural Wiskott-Aldrich syndrome protein (N-WASP) and actin-related protein-3 (Arp3) as well as cortical F-actin polymerization by a mechanism that is insensitive to the PI 3-kinase inhibitor wortmannin. Expression of the dominant inhibitory N-WASP-DeltaWA protein lacking the Arp and actin binding regions attenuates the cortical F-actin rearrangements by insulin in these cells. Remarkably, the N-WASP-DeltaWA protein also inhibits insulin action on GLUT4 translocation, indicating dependence of GLUT4 recycling on N-WASP-directed cortical F-actin assembly. TC10 exhibits sequence similarity to Cdc42 and has been reported to bind N-WASP. We show the inhibitory TC10 (T31N) mutant, which abrogates insulin-stimulated GLUT4 translocation and glucose transport, also inhibits both cortical localization of N-WASP and F-actin formation in response to insulin. These findings reveal that N-WASP likely functions downstream of TC10 in a PI 3-kinase-independent insulin signaling pathway to mobilize cortical F-actin, which in turn promotes GLUT4 responsiveness to insulin.</p>
dc.identifier.submissionpathoapubs/732
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages509-15


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