Signal Termination

An Off Switch

Science's STKE  10 Apr 2001:
Vol. 2001, Issue 77, pp. tw11
DOI: 10.1126/stke.2001.77.tw11

Sanjuán et al. investigated the role of diacylglycerol kinase α (DGKα) in the termination of signaling in T cells. The studies were performed in a T cell line that heterologously expresses a muscarinic acetylcholine receptor (which activates phospholipase C via a G protein) and measured the expression of CD69 as a marker of diacylglycerol (DAG)-mediated signaling. Stimulation of the cells with the muscarinic receptor agonist carbachol led to increased production of phosphatidic acid (the product of DGKα action on DAG), transient redistribution of DGKα-labeled with green fluorescent protein to the plasma membrane, and increased expression of CD69. Deletion of the calcium-binding EF hand domains of DGKα resulted in constitutive association of DGKα with the plasma membrane, enhanced enzymatic activity, and suppression of CD69 expression compared to that in cells expressing wild-type DGKα treated with carbachol. Activation of DGKα appeared to require two simultaneous signals: an increase in cytosolic calcium concentration and activation of tyrosine kinases.

M. A. Sanjuán, D. R. Jones, M. Izquierdo, I. Mérida, Role of diacylglycerol kinase α in the attenuation of receptor signaling. J. Cell Biol. 153, 207-219 (2001). [Abstract] [Full Text]