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pubmed:abstractText |
Diacylglycerol kinase (DGK) has been suggested to be a pharmacological target of D-alpha-tocopherol for diabetic renal dysfunctions. However, the DGK subtypes involved in the D-alpha-tocopherol-induced improvement of diabetic renal dysfunctions and the activation mechanisms of DGK by D-alpha-tocopherol are still unknown. Therefore, using GFP-tagged DGKalpha, beta, gamma, epsilon and zeta, we analyzed their response to D-alpha-tocopherol and its derivatives. Only DGKalpha was translocated from the cytoplasm to the plasma membrane with elevation of kinase activity. In addition, troglitazone and trolox possessing 'chroman ring' similarly to D-alpha-tocopherol, induced the subtype-specific translocation of DGKalpha. Furthermore, the translocation of DGKalpha was abolished by pretreatment with tyrosine kinase inhibitors or by mutation on Tyr-334 of the kinase (YF mutant). D-alpha-tocopheryl succinate enhanced the Src-mediated tyrosine phosphorylation of wild-type DGKalpha but the same reagent did not enhance that of the YF mutant. These results demonstrate that tyrosine phosphorylation on Tyr-334 and chroman ring are important for the D-alpha-tocopherol-induced translocation of DGKalpha.
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pubmed:affiliation |
Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Nadaku, Kobe 657-8501, Japan.
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