Ceramide-1-phosphate: the "missing" link in eicosanoid biosynthesis and inflammation.
It has been over a decade since ceramide kinase (CERK) and its product, ceramide-1-phosphate (C1P), were first reported. Since itscloning, in 2002, CERK has been the subject of an explosion of publications concerning various signal transduction pathways. The roles of this previously overlooked enzyme, as well as those of its product C1P, continue to expand, and their regulatory functions in the production of eicosanoid inflammatory mediators are proving essential to fundamental signal transduction pathways. In particular, C1P is required for the activation and translocation of cPLA(2)alpha, the initial rate-limiting step of eicosanoid synthesis. The potential for inhibitors of CERK to offer a new generation of anti-inflammatory and anti-cancer therapeutics is especially deserving of further study.
Lamour
Nadia F
NF
Department of Biochemistry, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, VA 23298, USA.
Chalfant
Charles E
CE
D000818:Animals; D002518:Ceramides / Q000502:physiology*; D015777:Eicosanoids / Q000096:biosynthesis*; D004789:Enzyme Activation; D054513:Group IV Phospholipases A2; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D015398:Signal Transduction
D002518:Ceramides; D015777:Eicosanoids; C065576:ceramide 1-phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase; D010741:Phospholipases A; D054513:Group IV Phospholipases A2