Ceramide kinase: the first decade.
It has been some 20 years since the initial discovery of ceramide 1-phosphate (C1P) and nearly a decade since ceramide kinase (CERK) was cloned. Many studies have shown that C1P is important for membrane biology and for the regulation of membrane-bound proteins, and the CERK enzyme has appeared to be tightly regulated in order to control both ceramide levels and production of C1P. Furthermore, C1P made by CERK has emerged as a genuine signalling entity. However, it represents only part of the C1P pool that is available in the cell, therefore suggesting that alternative unknown C1P-producing mechanisms may also play a role. Recent technological developments for measuring complex sphingolipids in biological samples, together with the availability of Cerk-deficient animals as well as potent CERK inhibitors, have now provided new grounds for investigating C1P biology further. Here, we will review the current understanding of CERK and C1P in terms of biochemistry and functional implications, with particular attention to C1P produced by CERK.
Novartis Institutes for BioMedical Research, CH-4056 Basle, Switzerland. frederic.bornancin@novartis.com
Frédéric
F
Bornancin
D020816:Amino Acid Motifs; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D009420:Nervous System / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism; D015854:Up-Regulation
D002518:Ceramides; D018836:Inflammation Mediators; D013107:Sphingolipids; C065576:ceramide 1-phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase