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Journal of Lipid Research, Vol. 50, S35-S39, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Enzymology

Signaling at the membrane interface by the DGK/SK enzyme family

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

^* Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205
Departments of Medicine, Biochemistry and Molecular Biology, and Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202

This work was supported by Grant GM059251 (D.M.R.) and Grant CA111987 (B.W.W.) from the National Institutes of Health.

Published, JLR Papers in Press, December 9, 2008.

¹ To whom correspondence should be addressed. e-mail: draben{at}jhmi.edu (D.M.R.); b0watt01{at}gwise.louisville.edu (B.W.W.)

ABSTRACT

The sphingosine (SK) and diacylglycerol (DGK) kinases have become the subject of considerable focus recently due to their involvement as signaling enzymes in a variety of important biological processes. These lipid signaling kinases are closely related by sequence as well as functional properties. These enzymes are soluble, yet their substrates are hydrophobic. Therefore, they must act at the membrane interface. Second, for both of these enzyme families, their substrates (diacylglycerol for DGKs, sphingosine for SKs) as well as their products (phosphatidic acid for DGK, sphingosine-1-phosphate for SK) have signaling function. To understand how the signaling processes emanating from these kinases are regulated it is critical to understand the fundamental mechanisms that control their enzymatic activity. This is particularly true for the rational design of small molecules that would be useful as therapeutic compounds. Here we summarize enzymological properties of the diacylglycerol and SKs. Further, because the three-dimensional structure of the eukaryotic members of this family has yet to be determined, we discuss what can be gleaned from the recently reported structures of related prokaryotic members of this enzyme family.

Supplementary key words diacylglycerol kinase • sphingosine • kinase • interfacial enzymology • surface dilution kinetics

Abbreviations: ATP, adenosine triphosphate; CRD, cysteine rich domain; CTP, cytosine triphosphate; DAG, diacylglycerol; DGK, diacylglycerol kinase; PA, phosphatidic acid; PKB, protein kinase B; PLD, phospholipase D; PS, phosphatidylserine; SK, spingosine kinase

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