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J Membr Biol
2014 Aug 01;2478:713-20. doi: 10.1007/s00232-014-9695-3.
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Upregulation of excitatory amino acid transporters by coexpression of Janus kinase 3.
Warsi J
,
Luo D
,
Elvira B
,
Jilani K
,
Shumilina E
,
Hosseinzadeh Z
,
Lang F
.
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Janus kinase 3 (JAK3) contributes to cytokine receptor signaling, confers cell survival and stimulates cell proliferation. The gain of function mutation JAK3(A572V) is found in acute megakaryoplastic leukemia. Replacement of ATP coordinating lysine by alanine yields inactive JAK3(K855A). Most recent observations revealed the capacity of JAK3 to regulate ion transport. This study thus explored whether JAK3 regulates glutamate transporters EAAT1-4, carriers accomplishing transport of glutamate and aspartate in a variety of cells including intestinal cells, renal cells, glial cells, and neurons. To this end, EAAT1, 2, 3, or 4 were expressed in Xenopus oocytes with or without additional expression of mouse wild-type JAK3, constitutively active JAK3(A568V) or inactive JAK3(K851A), and electrogenic glutamate transport was determined by dual electrode voltage clamp. Moreover, Ussing chamber was employed to determine electrogenic glutamate transport in intestine from mice lacking functional JAK3 (jak3(-/-)) and from corresponding wild-type mice (jak3(+/+)). As a result, in EAAT1, 2, 3, or 4 expressing oocytes, but not in oocytes injected with water, addition of glutamate to extracellular bath generated an inward current (Ig), which was significantly increased following coexpression of JAK3. Ig in oocytes expressing EAAT3 was further increased by JAK3(A568V) but not by JAK3(K851A). Ig in EAAT3 + JAK3 expressing oocytes was significantly decreased by JAK3 inhibitor WHI-P154 (22 µM). Kinetic analysis revealed that JAK3 increased maximal Ig and significantly reduced the glutamate concentration required for half maximal Ig (Km). Intestinal electrogenic glutamate transport was significantly lower in jak3(-/-) than in jak3(+/+) mice. In conclusion, JAK3 is a powerful regulator of excitatory amino acid transporter isoforms.
Alesutan,
Upregulation of Na-coupled glucose transporter SGLT1 by Tau tubulin kinase 2.
2012, Pubmed,
Xenbase
Alesutan,
Upregulation of Na-coupled glucose transporter SGLT1 by Tau tubulin kinase 2.
2012,
Pubmed
,
Xenbase
Almilaji,
Down-regulation of Na/K+ atpase activity by human parvovirus B19 capsid protein VP1.
2013,
Pubmed
,
Xenbase
Almilaji,
Upregulation of Na+,Cl(-)-coupled betaine/γ-amino-butyric acid transporter BGT1 by Tau tubulin kinase 2.
2013,
Pubmed
,
Xenbase
Amara,
Excitatory amino acid transporters: keeping up with glutamate.
2002,
Pubmed
Ananthakrishnan,
JAK-STAT pathway in cardiac ischemic stress.
2005,
Pubmed
Barnett,
Antisense knockdown of GLAST, a glial glutamate transporter, compromises retinal function.
2000,
Pubmed
Beart,
Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement.
2007,
Pubmed
Berger,
Comparative analysis of glutamate transporter expression in rat brain using differential double in situ hybridization.
1998,
Pubmed
Bogatikov,
Up-regulation of amino acid transporter SLC6A19 activity and surface protein abundance by PKB/Akt and PIKfyve.
2012,
Pubmed
,
Xenbase
Castagna,
Molecular characteristics of mammalian and insect amino acid transporters: implications for amino acid homeostasis.
1997,
Pubmed
,
Xenbase
Cholet,
Similar perisynaptic glial localization for the Na+,K+-ATPase alpha 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex.
2002,
Pubmed
Collin,
Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight.
2003,
Pubmed
Cooper,
Gene and protein expression in the epididymis of infertile c-ros receptor tyrosine kinase-deficient mice.
2003,
Pubmed
Cornejo,
JAK3: a two-faced player in hematological disorders.
2009,
Pubmed
Derouiche,
Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST and GS in transmitter clearance.
1995,
Pubmed
Domercq,
Expression of glutamate transporters in rat optic nerve oligodendrocytes.
1999,
Pubmed
Dërmaku-Sopjani,
Down-regulation of the Na+-coupled phosphate transporter NaPi-IIa by AMP-activated protein kinase.
2013,
Pubmed
,
Xenbase
Fainstein,
Neural precursor cells inhibit multiple inflammatory signals.
2008,
Pubmed
Furness,
Immunocytochemical localization of a high-affinity glutamate-aspartate transporter, GLAST, in the rat and guinea-pig cochlea.
1997,
Pubmed
Furuta,
Expression of glutamate transporter subtypes during normal human corticogenesis and type II lissencephaly.
2005,
Pubmed
Furuta,
Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4.
1997,
Pubmed
Gaillet,
Transient increase in the high affinity [3H]-L-glutamate uptake activity during in vitro development of hippocampal neurons in culture.
2001,
Pubmed
Ghoreschi,
Janus kinases in immune cell signaling.
2009,
Pubmed
Gibb,
A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis.
2007,
Pubmed
Gloy,
Amino acid transport in podocytes.
2000,
Pubmed
Gras,
EAAT expression by macrophages and microglia: still more questions than answers.
2012,
Pubmed
Gray,
Glutamate does not play a major role in controlling bone growth.
2001,
Pubmed
Haan,
Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors.
2011,
Pubmed
Henrion,
Overlapping cardiac phenotype associated with a familial mutation in the voltage sensor of the KCNQ1 channel.
2012,
Pubmed
,
Xenbase
Hosseinzadeh,
Downregulation of ClC-2 by JAK2.
2012,
Pubmed
,
Xenbase
Hosseinzadeh,
Upregulation of peptide transporters PEPT1 and PEPT2 by Janus kinase JAK2.
2013,
Pubmed
,
Xenbase
Hosseinzadeh,
Regulation of the glutamate transporters by JAK2.
2011,
Pubmed
,
Xenbase
Hosseinzadeh,
Down-regulation of the myoinositol transporter SMIT by JAK2.
2012,
Pubmed
,
Xenbase
Huang,
Climbing fiber activation of EAAT4 transporters and kainate receptors in cerebellar Purkinje cells.
2004,
Pubmed
Imada,
The Jak-STAT pathway.
2000,
Pubmed
Johnston,
Signaling by IL-2 and related cytokines: JAKs, STATs, and relationship to immunodeficiency.
1996,
Pubmed
Kim,
MS-1020 is a novel small molecule that selectively inhibits JAK3 activity.
2010,
Pubmed
King,
Aspartate transporter expression and activity in hypertrophic rat heart and ischaemia-reperfusion injury.
2004,
Pubmed
Lawton,
Localization of the glutamate-aspartate transporter, GLAST, in rat taste buds.
2000,
Pubmed
Lee,
Localization, transport, and uptake of D-aspartate in the rat adrenal and pituitary glands.
2001,
Pubmed
Lehre,
The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain.
1998,
Pubmed
Li,
Identification of a glutamate/aspartate transporter in the rat cochlea.
1994,
Pubmed
Liva,
Signal transduction pathways induced by GM-CSF in microglia: significance in the control of proliferation.
1999,
Pubmed
Malinge,
Activating mutations in human acute megakaryoblastic leukemia.
2008,
Pubmed
Mason,
Mechanically regulated expression of a neural glutamate transporter in bone: a role for excitatory amino acids as osteotropic agents?
1997,
Pubmed
Matthews,
Placental anionic and cationic amino acid transporter expression in growth hormone overexpressing and null IGF-II or null IGF-I receptor mice.
1999,
Pubmed
Mia,
Downregulation of Kv1.5 K channels by the AMP-activated protein kinase.
2012,
Pubmed
,
Xenbase
Milton,
Expression of the glial glutamate transporter EAAT2 in the human CNS: an immunohistochemical study.
1997,
Pubmed
Miralles,
Na+ dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) in primary astrocyte cultures: effect of oxidative stress.
2001,
Pubmed
Nagel,
Microarray analysis of the global gene expression profile following hypothermia and transient focal cerebral ischemia.
2012,
Pubmed
Nakayama,
BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3.
2009,
Pubmed
Nieoullon,
The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?
2006,
Pubmed
Noorlander,
Distribution of glutamate transporters in the human placenta.
2004,
Pubmed
O'Kane,
Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal.
1999,
Pubmed
O'Shea,
Cytokine signaling in 2002: new surprises in the Jak/Stat pathway.
2002,
Pubmed
Orellana,
Role of the JAKs/STATs pathway in the intracellular calcium changes induced by interleukin-6 in hippocampal neurons.
2005,
Pubmed
Pakladok,
PIKfyve sensitivity of hERG channels.
2013,
Pubmed
,
Xenbase
Pathare,
Enhanced FGF23 serum concentrations and phosphaturia in gene targeted mice expressing WNK-resistant SPAK.
2012,
Pubmed
Pathare,
OSR1-sensitive renal tubular phosphate reabsorption.
2012,
Pubmed
,
Xenbase
Rainesalo,
GABA and glutamate transporters are expressed in human platelets.
2005,
Pubmed
Redecker,
Immunohistochemical study of the glutamate transporter proteins GLT-1 and GLAST in rat and gerbil pineal gland.
2000,
Pubmed
Rothstein,
Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate.
1996,
Pubmed
Rothstein,
Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression.
2005,
Pubmed
Rothstein,
Localization of neuronal and glial glutamate transporters.
1994,
Pubmed
Sandhu,
Characterization of astrocytes derived from human NTera-2/D1 embryonal carcinoma cells.
2002,
Pubmed
Schmitt,
Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain.
2003,
Pubmed
Schniepp,
Retinal colocalization and in vitro interaction of the glutamate transporter EAAT3 and the serum- and glucocorticoid-inducible kinase SGK1 [correction].
2004,
Pubmed
,
Xenbase
Shashidharan,
Immunohistochemical localization of the neuron-specific glutamate transporter EAAC1 (EAAT3) in rat brain and spinal cord revealed by a novel monoclonal antibody.
1997,
Pubmed
Shuai,
Regulation of JAK-STAT signalling in the immune system.
2003,
Pubmed
Takumi,
Discrete cellular and subcellular localization of glutamine synthetase and the glutamate transporter GLAST in the rat vestibular end organ.
1997,
Pubmed
Uckun,
Targeting JAK3 tyrosine kinase-linked signal transduction pathways with rationally-designed inhibitors.
2007,
Pubmed
Ullensvang,
Differential developmental expression of the two rat brain glutamate transporter proteins GLAST and GLT.
1997,
Pubmed
Umbach,
Intestinal Na+ loss and volume depletion in JAK3-deficient mice.
2013,
Pubmed
Walters,
Activating alleles of JAK3 in acute megakaryoblastic leukemia.
2006,
Pubmed
Wang,
Sequential activation of JAKs, STATs and xanthine dehydrogenase/oxidase by hypoxia in lung microvascular endothelial cells.
2008,
Pubmed
Warsi,
Effect of Janus kinase 3 on the peptide transporters PEPT1 and PEPT2.
2013,
Pubmed
,
Xenbase
Yamaoka,
Jak3 negatively regulates dendritic-cell cytokine production and survival.
2005,
Pubmed
Zoia,
Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease.
2004,
Pubmed
de Totero,
The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways.
2008,
Pubmed
van Landeghem,
Expression of PACAP and glutamate transporter proteins in satellite oligodendrocytes of the human CNS.
2007,
Pubmed
