Biochem Biophys Res Commun 2004 Nov 26;3244:1242-8. doi: 10.1016/j.bbrc.2004.09.193.

Stimulation of the EAAT4 glutamate transporter by SGK protein kinase isoforms and PKB.

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The serum and glucocorticoid inducible kinase (SGK) 1 is expressed in brain tissue and upregulated by ischemia, neuronal excitation, and dehydration. The present study has been performed to elucidate the expression of SGK1 in cerebellar Purkinje cells and to explore whether it influences the colocalized glutamate transporter EAAT4. Intense SGK1 staining was observed in Purkinje cells following 48h of water deprivation. The kinase activates glutamate induced current (I(GLU)) in Xenopus oocytes heterologously expressing EAAT4, an effect mimicked by its isoforms SGK2, 3 and PKB. I(GLU) was decreased by the ubiquitin ligase Nedd4-2, an effect partially but not completely reversed by additional coexpression of the SGK kinase isoforms or PKB. According to immunohistochemistry EAAT4 protein abundance in the cell membrane was enhanced by SGK1 and decreased by Nedd4-2. In conclusion, SGK1 expression is upregulated by ischemia, excitation, and dehydration in cerebellar Purkinje cells. The upregulation of SGK1 may serve to stimulate EAAT4 and thus to reduce neuroexcitotoxicity.

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Species referenced: Xenopus
Genes referenced: akt1 nedd4 nedd4l ptk2b sgk1 sgk2 slc1a6