Signaling at the membrane interface by the DGK/SK enzyme family.
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.
Raben
Daniel M
DM
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. draben@jhmi.edu.
Wattenberg
Binks W
BW
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D019852:Diacylglycerol Kinase / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D050356:Lipid Metabolism; D009097:Multienzyme Complexes / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction; D013430:Sulfate Adenylyltransferase / Q000737:chemistry / Q000145:classification / Q000378:metabolism*
D009097:Multienzyme Complexes; C113697:sulfurylase kinase; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; D013430:Sulfate Adenylyltransferase