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Importance of chroman ring and tyrosine phosphorylation in the subtype‐specific translocation and activation of diacylglycerol kinase α by d ‐α‐tocopherol
Author(s) -
FukunagaTakenaka Rika,
Shirai Yasuhito,
Yagi Keiko,
Adachi Naoko,
Sakai Norio,
Merino Ernesto,
Merida Isabel,
Saito Naoaki
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00842.x
Subject(s) - diacylglycerol kinase , phosphorylation , biology , tyrosine phosphorylation , tyrosine kinase , chromosomal translocation , biochemistry , tyrosine , kinase , microbiology and biotechnology , protein kinase c , signal transduction , gene
Diacylglycerol kinase (DGK) has been suggested to be a pharmacological target of d ‐α‐tocopherol for diabetic renal dysfunctions. However, the DGK subtypes involved in the d ‐α‐tocopherol‐induced improvement of diabetic renal dysfunctions and the activation mechanisms of DGK by d ‐α‐tocopherol are still unknown. Therefore, using GFP‐tagged DGKα, β, γ, ɛ and ζ, we analyzed their response to d ‐α‐tocopherol and its derivatives. Only DGKα 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 ‐α‐tocopherol, induced the subtype‐specific translocation of DGKα. Furthermore, the translocation of DGKα was abolished by pretreatment with tyrosine kinase inhibitors or by mutation on Tyr‐334 of the kinase (YF mutant). d ‐α‐tocopheryl succinate enhanced the Src‐mediated tyrosine phosphorylation of wild‐type DGKα 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 ‐α‐tocopherol‐induced translocation of DGKα.