Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell
2015 Jun 04;585:845-53. doi: 10.1016/j.molcel.2015.04.015.
Show Gene links
Show Anatomy links
A Protein Kinase C Phosphorylation Motif in GLUT1 Affects Glucose Transport and is Mutated in GLUT1 Deficiency Syndrome.
Lee EE
,
Ma J
,
Sacharidou A
,
Mi W
,
Salato VK
,
Nguyen N
,
Jiang Y
,
Pascual JM
,
North PE
,
Shaul PW
,
Mettlen M
,
Wang RC
.
???displayArticle.abstract???
Protein kinase C has been implicated in the phosphorylation of the erythrocyte/brain glucose transporter, GLUT1, without a clear understanding of the site(s) of phosphorylation and the possible effects on glucose transport. Through in vitro kinase assays, mass spectrometry, and phosphospecific antibodies, we identify serine 226 in GLUT1 as a PKC phosphorylation site. Phosphorylation of S226 is required for the rapid increase in glucose uptake and enhanced cell surface localization of GLUT1 induced by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Endogenous GLUT1 is phosphorylated on S226 in primary endothelial cells in response to TPA or VEGF. Several naturally occurring, pathogenic mutations that cause GLUT1 deficiency syndrome disrupt this PKC phosphomotif, impair the phosphorylation of S226 in vitro, and block TPA-mediated increases in glucose uptake. We demonstrate that the phosphorylation of GLUT1 on S226 regulates glucose transport and propose that this modification is important in the physiological regulation of glucose transport.
Antal,
Cancer-associated protein kinase C mutations reveal kinase's role as tumor suppressor.
2015, Pubmed
Antal,
Cancer-associated protein kinase C mutations reveal kinase's role as tumor suppressor.
2015,
Pubmed
Arsov,
Glucose transporter 1 deficiency in the idiopathic generalized epilepsies.
2012,
Pubmed
,
Xenbase
Barnes,
Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK).
2002,
Pubmed
Birnbaum,
Transformation of rat fibroblasts by FSV rapidly increases glucose transporter gene transcription.
1987,
Pubmed
Castagna,
Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.
1982,
Pubmed
Cura,
Acute modulation of sugar transport in brain capillary endothelial cell cultures during activation of the metabolic stress pathway.
2010,
Pubmed
De Vivo,
Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay.
1991,
Pubmed
Deng,
Crystal structure of the human glucose transporter GLUT1.
2014,
Pubmed
Deziel,
Phosphorylation of the human erythrocyte glucose transporter by protein kinase C: localization of the site of in vivo and in vitro phosphorylation.
1989,
Pubmed
Driedger,
The effect of phorbol diesters on chicken embryo fibroblasts.
1977,
Pubmed
Edelstein,
Computer control of microscopes using µManager.
2010,
Pubmed
Flier,
Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes.
1987,
Pubmed
Gibbs,
The glucose transporter in 3T3-L1 adipocytes is phosphorylated in response to phorbol ester but not in response to insulin.
1986,
Pubmed
Hresko,
Topology of the Glut 1 glucose transporter deduced from glycosylation scanning mutagenesis.
1994,
Pubmed
,
Xenbase
Klepper,
Glut1 deficiency syndrome and novel ketogenic diets.
2013,
Pubmed
Lee,
Membrane effects of tumor promoters: stimulation of sugar uptake in mammalian cell cultures.
1979,
Pubmed
Leen,
Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder.
2010,
Pubmed
Mann,
Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells.
2003,
Pubmed
Mullen,
Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency.
2010,
Pubmed
Mîinea,
Stoichiometry of site-specific protein phosphorylation estimated with phosphopeptide-specific antibodies.
2003,
Pubmed
Nishikawa,
Determination of the specific substrate sequence motifs of protein kinase C isozymes.
1997,
Pubmed
Nishimura,
Kinetics of GLUT1 and GLUT4 glucose transporters expressed in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
O'Brien,
Hexose transport in undifferentiated and differentiated BALB/c 3T3 preadipose cells: effects 12-O-tetradecanoylphorbol-13-acetate and insulin.
1982,
Pubmed
Seidner,
GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier.
1998,
Pubmed
Siska,
PKCs Sweeten Cell Metabolism by Phosphorylation of Glut1.
2015,
Pubmed
Sone,
Enhancement of glucose transport by vascular endothelial growth factor in retinal endothelial cells.
2000,
Pubmed
Suls,
Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1.
2009,
Pubmed
Tang,
Angiotensin II increases glucose uptake and glucose transporter-1 mRNA levels in astroglia.
1995,
Pubmed
Vergarajauregui,
Mucolipin 1 channel activity is regulated by protein kinase A-mediated phosphorylation.
2008,
Pubmed
Wang,
Functional studies of the T295M mutation causing Glut1 deficiency: glucose efflux preferentially affected by T295M.
2008,
Pubmed
,
Xenbase
Weber,
GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak.
2008,
Pubmed
,
Xenbase
Wieman,
Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking.
2007,
Pubmed
Witters,
Phosphorylation of the glucose transporter in vitro and in vivo by protein kinase C.
,
Pubmed
Yamamoto,
Over-expression of facilitative glucose transporter genes in human cancer.
1990,
Pubmed
Younes,
Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers.
1996,
Pubmed
