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Um novo mecanismo molecular para a regulação do transportador de glicose GLUT1

dc.contributor.authorMendes, A.I.
dc.contributor.authorMatos, P.
dc.contributor.authorMoniz, S.
dc.contributor.authorJordan, P.
dc.date.accessioned2011-10-04T14:58:17Z
dc.date.available2011-10-04T14:58:17Z
dc.date.issued2011-01
dc.descriptionPrémio de Investigação Básicapor
dc.description.abstractOne mechanism by which 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 storage vesicles through inactivation of the Rab GTPase activating protein TBC1D4, also known as AS160. Using protein biochemical techniques we analysed complex formation between TBC1D4 and protein kinase WNK1 in human embryonic kidney (HEK293) cells. We found that WNK1 associates in a protein complex with TBC1D4 and phosphorylates TBC1D4 in vitro. This resulted in increased expression levels of the constitutive glucose transporter GLUT1 at the cell surface. 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 molecular pathway regulating constitutive glucose uptake via GLUT1, the expression level of which is related to several human diseases. This pathway may be important in the cellular response to insulin.por
dc.description.sponsorshipFCTpor
dc.identifier.urihttp://hdl.handle.net/10400.18/241
dc.language.isoporpor
dc.peerreviewedyespor
dc.relationPOCI_PPCDT/SAU-MMO/56439/04por
dc.subjectVias de Transdução de Sinal e Patologias Associadaspor
dc.subjectProteina cinasepor
dc.subjectGlucosepor
dc.subjectDiabetespor
dc.subjectWNKpor
dc.subjectTransporte membranarpor
dc.titleUm novo mecanismo molecular para a regulação do transportador de glicose GLUT1por
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceTroia, 27-30 de Janeiro de 2011por
oaire.citation.title62ª Reunião Anual da Sociedade Portuguesa de Endocrinologia e Doenças Metabólicaspor
rcaap.rightsopenAccesspor
rcaap.typeconferenceObjectpor

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