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Titolo:
Functional regulation of gamma-aminobutyric acid transporters by direct tyrosine phosphorylation
Autore:
Law, RM; Stafford, A; Quick, MW;
Indirizzi:
Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Neurobiol, Birmingham, AL 35294 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 31, volume: 275, anno: 2000,
pagine: 23986 - 23991
SICI:
0021-9258(20000804)275:31<23986:FROGAT>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; CELL-SURFACE EXPRESSION; BRAIN GABA TRANSPORTER; RAT HIPPOCAMPAL SLICE; SEROTONIN TRANSPORTERS; GLUTAMATE TRANSPORTERS; DOPAMINE TRANSPORTER; XENOPUS-OOCYTES; MICE LACKING; CHANNELS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Quick, MW Univ Alabama, Dept Neurobiol, CIRC 446,1719 6th Ave S, Birmingham, AL 35294 USA Univ Alabama CIRC 446,1719 6th Ave S Birmingham AL USA 35294 USA
Citazione:
R.M. Law et al., "Functional regulation of gamma-aminobutyric acid transporters by direct tyrosine phosphorylation", J BIOL CHEM, 275(31), 2000, pp. 23986-23991

Abstract

Tyrosine phosphorylation regulates multiple cell signaling pathways and functionally modulates a number of ion channels and receptors, Neurotransmitter transporters, which act to clear transmitter from the synaptic cleft, are regulated by multiple second messenger pathways that exert their effects,at least in part, by causing a redistribution of the transporter protein to or from the cell surface. To test the hypothesis that tyrosine phosphorylation affects transporter function and to determine its mechanism of action, we examined the regulation of the rat brain gamma-aminobutyric acid (GABA) transporter GAT1 expressed endogenously in hippocampal neurons and expressed heterologously in Chinese hamster ovary cells. Inhibitors of tyrosine kinases decreased GABA uptake; inhibitors of tyrosine phosphatases increasedGABA uptake. The decrease in uptake seen with tyrosine kinase inhibitors was correlated with a decrease in tyrosine phosphorylation of GAT1 and resulted in a redistribution of the transporter from the cell surface to intracellular locations. A mutant GAT1 construct that was refractory to tyrosine phosphorylation could not be regulated by tyrosine kinase inhibitors. Activators of protein kinase C, which are known to cause a redistribution of GAT1from the cell surface, were additive to the effects of tyrosine kinase inhibitors suggesting that multiple signaling pathways control transporter redistribution. Application of brain-derived neurotrophic factor, which activates receptor tyrosine kinases, up-regulated GAT1 function suggesting one potential trigger for the cellular regulation of GAT1 signaling by tyrosine phosphorylation, These data support the hypothesis that transporter expression and function is controlled by the interplay of multiple cell signaling cascades.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/06/20 alle ore 01:37:16