The sphingosine and diacylglycerol kinase superfamily of signaling kinases: localization as a key to signaling function.
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.
Wattenberg
Binks W
BW
Department of Medicine, University of Louisville, Louisville, KY, USA. b0watt01@louisville.edu
Pitson
Stuart M
SM
Raben
Daniel M
DM
D000818:Animals; D019852:Diacylglycerol Kinase / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099157:Sphingosine Kinase
D019852:Diacylglycerol Kinase; D006133:Growth Substances; D007527:Isoenzymes; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D014409:Tumor Necrosis Factor-alpha; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate