Coincident regulation of PKC{delta} in human platelets by phosphorylation of Tyr 311} and Tyr 565} and phospholipase C signaling - Archive ouverte HAL Access content directly
Journal Articles Biochemical Journal Year : 2007

Coincident regulation of PKC{delta} in human platelets by phosphorylation of Tyr 311} and Tyr 565} and phospholipase C signaling

Kellie J Hall
  • Function : Author
Matthew L Jones
  • Function : Author
Alastair W Poole
  • Function : Correspondent author
  • PersonId : 870086

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Abstract

PKCδ plays a complex role in platelets, having both positive and negative signaling functions. It is phosphorylated on tyrosine in response to thrombin and collagen, and it has recently been shown that residue Y311 is phosphorylated in response to PAR1 and PAR4 receptor activation. Here we show Y311 and Y565 to be phosphorylated in response to thrombin, and have addressed the interplay between phosphorylation and the classical lipid-mediated activation of PKCδ. Phosphorylation of both Y311 and Y565 is dependent upon Src kinase and phospholipase C activity in response to thrombin. Importantly however, direct allosteric activation of PKCδ with phorbol myristate (PMA) also induced phosphorylation of Y311 and Y565, dependent upon Src kinases, but not phospholipase C. Membrane recruitment of PKCδ is essential for phosphorylation of the kinase on tyrosine, but tyrosine phosphorylation is not required for membrane recruitment of PKCδ. Both thrombin and PMA induce recruitment of PKCδ to the membrane, which for thrombin is by a PLC-dependent process. In order to address the functional role of tyrosine phosphorylation of PKCδ, we show phosphorylation to potentiate the activity of the kinase, although it does not play a role in membrane recruitment of the kinase. PKCδ is therefore regulated in a coincident fashion by PLC-dependent signals, recruiting it to the plasma membrane, and phosphorylation on tyrosine potentiating its activity.

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hal-00478760 , version 1 (30-04-2010)

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Kellie J Hall, Matthew L Jones, Alastair W Poole. Coincident regulation of PKC{delta} in human platelets by phosphorylation of Tyr 311} and Tyr 565} and phospholipase C signaling. Biochemical Journal, 2007, 406 (3), pp.501-510. ⟨10.1042/BJ20070244⟩. ⟨hal-00478760⟩

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