File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Regulation of glucose transporter 4 translocation by the rab guanosine triphosphatase-activating protein AS160/TBC1D4: Role of phosphorylation and membrane association

TitleRegulation of glucose transporter 4 translocation by the rab guanosine triphosphatase-activating protein AS160/TBC1D4: Role of phosphorylation and membrane association
Authors
Issue Date2008
PublisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/
Citation
Molecular Endocrinology, 2008, v. 22 n. 12, p. 2703-2715 How to Cite?
AbstractInsulin-stimulated translocation of the glucose transporter GLUT4 to the plasma membrane in muscle and fat cells depends on the phosphatidylinositide 3-kinase/Akt pathway. The downstream target AS160/TBC1D4 is phosphorylated upon insulin stimulation and contains a TBC domain (Tre-2/Bub2/Cdc16) that is present in most Rab guanosine triphosphatase-activating proteins. TBC1D4 associates with GLUT4-containing membranes under basal conditions and dissociates from membranes with insulin. Here we show that the association of TBC1D4 with membranes is required for its inhibitory action on GLUT4 translocation under basal conditions. Whereas the insulin-dependent dissociation of TBC1D4 from membranes was not required for GLUT4 translocation, its phosphorylation was essential. Many agonists that stimulate GLUT4 translocation failed to trigger TBC1D4 translocation to the cytosol, but in most cases these agonists stimulated TBC1D4 phosphorylation at T642, and their effects on GLUT4 translocation were inhibited by overexpression of the TBC1D4 phosphorylation mutant (TBC1D4-4P). We postulate that TBC1D4 acts to impede GLUT4 translocation by disarming a Rab protein found on GLUT4-containing-membranes and that phosphorylation of TBC1D4 per se is sufficient to overcome this effect, allowing GLUT4 translocation to the cell surface to proceed. Copyright © 2008 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/59172
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.195
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorStöckli, Jen_HK
dc.contributor.authorDavey, JRen_HK
dc.contributor.authorHohnenBehrens, Cen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorJames, DEen_HK
dc.contributor.authorRamm, Gen_HK
dc.date.accessioned2010-05-31T03:44:17Z-
dc.date.available2010-05-31T03:44:17Z-
dc.date.issued2008en_HK
dc.identifier.citationMolecular Endocrinology, 2008, v. 22 n. 12, p. 2703-2715en_HK
dc.identifier.issn0888-8809en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59172-
dc.description.abstractInsulin-stimulated translocation of the glucose transporter GLUT4 to the plasma membrane in muscle and fat cells depends on the phosphatidylinositide 3-kinase/Akt pathway. The downstream target AS160/TBC1D4 is phosphorylated upon insulin stimulation and contains a TBC domain (Tre-2/Bub2/Cdc16) that is present in most Rab guanosine triphosphatase-activating proteins. TBC1D4 associates with GLUT4-containing membranes under basal conditions and dissociates from membranes with insulin. Here we show that the association of TBC1D4 with membranes is required for its inhibitory action on GLUT4 translocation under basal conditions. Whereas the insulin-dependent dissociation of TBC1D4 from membranes was not required for GLUT4 translocation, its phosphorylation was essential. Many agonists that stimulate GLUT4 translocation failed to trigger TBC1D4 translocation to the cytosol, but in most cases these agonists stimulated TBC1D4 phosphorylation at T642, and their effects on GLUT4 translocation were inhibited by overexpression of the TBC1D4 phosphorylation mutant (TBC1D4-4P). We postulate that TBC1D4 acts to impede GLUT4 translocation by disarming a Rab protein found on GLUT4-containing-membranes and that phosphorylation of TBC1D4 per se is sufficient to overcome this effect, allowing GLUT4 translocation to the cell surface to proceed. Copyright © 2008 by The Endocrine Society.en_HK
dc.languageengen_HK
dc.publisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/en_HK
dc.relation.ispartofMolecular Endocrinologyen_HK
dc.rightsMolecular Endocrinology. Copyright © The Endocrine Society.en_HK
dc.subject.mesh3T3-L1 Cellsen_HK
dc.subject.meshAndrostadienes - pharmacologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCHO Cellsen_HK
dc.subject.meshCell Membrane - metabolism - physiologyen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCricetinaeen_HK
dc.subject.meshCricetulusen_HK
dc.subject.meshCytosol - drug effects - metabolismen_HK
dc.subject.meshGTPase-Activating Proteins - chemistry - metabolism - physiologyen_HK
dc.subject.meshGlucose Transporter Type 4 - metabolismen_HK
dc.subject.meshInsulin - pharmacologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMuscle Fibers, Skeletal - drug effects - metabolism - physiologyen_HK
dc.subject.meshPhosphorylation - drug effects - physiologyen_HK
dc.subject.meshProtein Kinase Inhibitors - pharmacologyen_HK
dc.subject.meshProtein Structure, Tertiary - physiologyen_HK
dc.subject.meshProtein Transport - drug effectsen_HK
dc.subject.meshTransport Vesicles - metabolism - physiologyen_HK
dc.subject.meshrab GTP-Binding Proteins - metabolismen_HK
dc.titleRegulation of glucose transporter 4 translocation by the rab guanosine triphosphatase-activating protein AS160/TBC1D4: Role of phosphorylation and membrane associationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0888-8809&volume=22&spage=2703&epage=15&date=2008&atitle=Regulation+of+glucose+transporter+4+translocation+by+the+Rab+guanosine+triphosphatase-activating+protein+AS160/TBC1D4:+role+of+phosphorylation+and+membrane+association.en_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1210/me.2008-0111en_HK
dc.identifier.pmid18801932-
dc.identifier.scopuseid_2-s2.0-56749173518en_HK
dc.identifier.hkuros157973en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56749173518&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume22en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2703en_HK
dc.identifier.epage2715en_HK
dc.identifier.isiWOS:000261305200010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridStöckli, J=17234006800en_HK
dc.identifier.scopusauthoridDavey, JR=8043218900en_HK
dc.identifier.scopusauthoridHohnenBehrens, C=15062874400en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridJames, DE=7401733057en_HK
dc.identifier.scopusauthoridRamm, G=7006307479en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats