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Protein kinase WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex

dc.contributor.authorMendes, Ana Isabel
dc.contributor.authorMatos, Paulo
dc.contributor.authorMoniz, Sónia
dc.contributor.authorJordan, Peter
dc.date.accessioned2011-09-14T14:56:09Z
dc.date.available2011-09-14T14:56:09Z
dc.date.issued2010-12-10
dc.description.abstractOne mechanism by which mammalian cells regulate the uptake of glucose is the number of glucose transporter proteins (GLUT) present at the plasma membrane. In insulin-responsive cells types, GLUT4 is released from intracellular stores through inactivation of the Rab GTPase activating protein Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4) (also known as AS160). Here we describe that TBC1D4 forms a protein complex with protein kinase WNK1 in human embryonic kidney (HEK293) cells. We show that WNK1 phosphorylates TBC1D4 in vitro and that the expression levels of WNK1 in these cells regulate surface expression of the constitutive glucose transporter GLUT1. WNK1 was found to increase the binding of TBC1D4 to regulatory 14-3-3 proteins while reducing its interaction with the exocytic small GTPase Rab8A. These effects were dependent on the catalytic activity because expression of a kinase-dead WNK1 mutant had no effect on binding of 14-3-3 and Rab8A, or on surface GLUT1 levels. Together, the data describe a pathway regulating constitutive glucose uptake via GLUT1, the expression level of which is related to several human diseases.por
dc.identifier.citationJ Biol Chem. 2010 Dec 10;285(50):39117-26. Epub 2010 Oct 11por
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/10400.18/171
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherAmerican Society for Biochemistry and Molecular Biologypor
dc.relation.publisherversionhttp://www.jbc.org/content/285/50/39117.abstractpor
dc.subjectVias de Transdução de Sinal e Patologias Associadaspor
dc.titleProtein kinase WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complexpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage39126por
oaire.citation.startPage39117por
oaire.citation.titleJournal of Biological Chemistrypor
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor

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