Role of phospholipase D in the activation of protein kinase D by lysophosphatidic acid

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• 作者：Kam ; Yoonseok ; Exton ; John H.
• 关键词：Phospholipase D ; Protein kinase D ; Phosphorylation ; Lysophosphatidic acid ; Diacylglycerol
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：February 27, 2004
• 年：2004
• 卷：315
• 期：1
• 页码：139-143
• 全文大小：196 K

文摘

Protein kinase D was auto-phosphorylated at Ser916 and trans-phosphorylated at Ser744/Ser748 in Rat-2 fibroblasts treated with lysophosphatidic acid. Both phosphorylations were inhibited by 1-butanol, which blocks phosphatidic acid formation by phospholipase D. The phosphorylations were also reduced in Rat-2 clones with decreased phospholipase D activity. Platelet-derived growth factor-induced protein kinase D phosphorylation showed a similar requirement for phospholipase D, but that induced by 4β-phorbol 12 myristate 13-acetate did not. Propranolol an inhibitor of diacylglycerol formation from phosphatidic acid blocked the phosphorylation of protein kinase D, whereas dioctanoylglycerol induced it. The temporal pattern of auto-phosphorylation of protein kinase D closely resembled that of phospholipase D activation and preceded the trans-phosphorylation by protein kinase C. These results suggest that protein kinase D is activated by lysophosphatidic acid through sequential phosphorylation and that diacylglycerol produced by PLD via phosphatidic acid is required for the autophosphorylation that occurs prior to protein kinase C-mediated phosphorylation.