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			PubMed Journals: Biochem J

  Source:		PMID: 15228384


    		Biochem J. 2004 Sep 15;382(Pt 3):957-66.
     
			The plasma membrane translocation of diacylglycerol
			kinase delta1 is negatively regulated by
			conventional protein kinase C-dependent
			phosphorylation at Ser-22 and Ser-26 within
			the pleckstrin homology domain.

			Imai S(1), Kai M, Yamada K, Kanoh H, Sakane
			F.

			Author Information
			(1) Department of Biochemistry, School of
			Medicine, Sapporo Medical University, South-1,
			West-17, Chuo-ku, Sapporo, 060-8556, Japan.

			DGK (diacylglycerol kinase) regulates the
			concentration of two bioactive lipids,
			diacylglycerol and phosphatidic acid. DGKdelta1
			or its PH (pleckstrin homology) domain alone
			has been shown to be translocated to the
			plasma membrane from the cytoplasm in PMA-treated
			cells. In the present study, we identified
			Ser-22 and Ser-26 within the PH domain as
			the PMA- and epidermal-growth-factor-dependent
			phosphorylation sites of DGKdelta1. Experiments
			in vitro and with intact cells suggested
			that the cPKC (conventional protein kinase
			C) phosphorylated these Ser residues directly.
			Puzzlingly, alanine/asparagine mutants at
			Ser-22 and Ser-26 of DGKdelta1 and its PH
			domain are still persistently translocated
			by PMA treatment, suggesting that the PH
			domain phosphorylation is not responsible
			for the enzyme translocation and that the
			translocation was caused by a PMA-dependent,
			but cPKC-independent, process yet to be
			identified. Interestingly, the aspartate
			mutation, which mimics phosphoserine, at
			Ser-22 or Ser-26, inhibited the translocation
			of full-length DGKdelta1 and the PH domain
			markedly, suggesting that the phosphorylation
			regulates negatively the enzyme translocation.
			Our results provide evidence of the phosphorylation
			of the DGKdelta1 PH domain by cPKC, and
			suggest that the phosphorylation is involved
			in the control of subcellular localization
			of DGKdelta1.

			DOI: 10.1042/BJ20040681 PMCID: PMC1133971
			PMID: 15228384 [Indexed for MEDLINE]

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