TY - JOUR
T1 - Regulation of diacylglycerol kinase α by phosphoinositide 3-kinase lipid products
AU - Ciprés, Angel
AU - Carrasco, Silvia
AU - Merino, Ernesto
AU - Díaz, Ernesto
AU - Krishna, U. Murali
AU - Falck, John R.
AU - Martínez-A, Carlos
AU - Mérida, Isabel
PY - 2003/9/12
Y1 - 2003/9/12
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M305635200
DO - 10.1074/jbc.M305635200
M3 - Article
C2 - 12832407
AN - SCOPUS:0042817949
SN - 0021-9258
VL - 278
SP - 35629
EP - 35635
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -