Regulation of diacylglycerol kinase α by phosphoinositide 3-kinase lipid products

Angel Ciprés, Silvia Carrasco, Ernesto Merino, Ernesto Díaz, U. Murali Krishna, John R. Falck, Carlos Martínez-A, Isabel Mérida

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42 Scopus citations

Abstract

Diacylglycerol kinase α (DAGKα), like all type I DAGKs, has calcium regulatory motifs that act as negative regulators of enzyme activity and localization. Accordingly, DAGKα is activated by phospholipase C-coupled receptors in a calcium-dependent manner. One of the first functions attributed to DAGKα in lymphocytes was that of regulating interleukin 2-induced cell cycle entry. Interleukin-2 nonetheless exerts its action in the absence of cytosolic calcium increase. We have studied alternative receptor-derived signals to explain calcium-independent DAGKα activation, and show that DAGKα is stimulated by Src-like kinase-dependent phosphoinositide 3 kinase (PI3K) activation in lymphocytes. Our results demonstrate that, in vivo, the increase in cellular levels of PI3K products is sufficient to induce DAGKα activation, allowing DAGKα relocation to the intact lymphocyte plasma membrane. This activation is isoform-specific, because other type I DAGKs are not subject to this type of regulation. These studies are the first to describe a pathway in which, in the absence of receptor-regulated calcium increase, DAGKα activation and membrane localization is a direct consequence of PI3K activation.

Original languageEnglish (US)
Pages (from-to)35629-35635
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number37
DOIs
StatePublished - Sep 12 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ciprés, A., Carrasco, S., Merino, E., Díaz, E., Krishna, U. M., Falck, J. R., Martínez-A, C., & Mérida, I. (2003). Regulation of diacylglycerol kinase α by phosphoinositide 3-kinase lipid products. Journal of Biological Chemistry, 278(37), 35629-35635. https://doi.org/10.1074/jbc.M305635200