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Journal of Lipid Research, Vol. 47, 1128-1139, June 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Review

The sphingosine and diacylglycerol kinase superfamily of signaling kinases: localization as a key to signaling function

Binks W. Wattenberg^1,*, Stuart M. Pitson and Daniel M. Raben

^* Departments of Medicine and Biochemistry and Molecular Biology, University of Louisville, Louisville, KY
Hanson Institute, Division of Human Immunology, Institute for Medical and Veterinary Science, Adelaide, South Australia, Australia
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD

Published, JLR Papers in Press, March 6, 2006.

¹ To whom correspondence should be addressed. e-mail: b0watt01{at}louisville.edu

The sphingosine and diacylglycerol kinases form a superfamily of structurally related lipid signaling kinases. One of the striking features of these kinases is that although they are clearly involved in agonist-mediated signaling, this signaling is accomplished with only a moderate (and sometimes no) increase in the enzymatic activity of the enzymes. Here, we summarize findings that indicate that signaling by these kinases is strongly dependent on their localization to specific intracellular sites rather than on increases in enzyme activity. Both the substrates and products of these enzymes are bioactive lipids. Moreover, many of the metabolic enzymes that act on these lipids are found in specific organelles. Therefore, changes in the membrane localization of these signaling kinases have profound effects not only on the production of signaling lipid phosphates but also on the metabolism of the upstream signaling lipids.

Abbreviations: CRD, cysteine-rich domain; DAG, diacylglycerol; DGK, diacylglycerol kinase; ERK2, extracellular signal-regulated kinase-2; K_cat, (V_max/enzyme concentration); PA, phosphatidic acid; PI, phosphatidylinositol; PIP₂, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; PS, phosphatidylserine; SK, sphingosine kinase; TNF-, tumor necrosis factor-

Supplementary key words Sphingosine-1-phosphate • phosphatidic acid • ceramide • subcellular compartmentalization • signal transduction • lipid kinases

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