The Role of Ceramide-1-Phosphate in Biological Functions
In mammalian cells, cermide-1-phosphate (C1P) is produced via the ATP-dependent mechanism of converting ceramide to C1P by the enzyme, ceramide kinase (CERK). CERK was first described as a calcium-stimulated lipid kinase that co-purified with brain synapt
- PDF / 272,206 Bytes
- 14 Pages / 439.37 x 666.142 pts Page_size
- 18 Downloads / 178 Views
Contents 1 Ceramide-1-Phosphate: The Early Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 C1P in Cell Growth and Survival: A Pro-survival Player . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 C1P in Immunity and Inflammation: “The Missing Link” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
154 155 157 162
Abstract In mammalian cells, cermide-1-phosphate (C1P) is produced via the ATP-dependent mechanism of converting ceramide to C1P by the enzyme, ceramide kinase (CERK). CERK was first described as a calcium-stimulated lipid kinase that co-purified with brain synaptic vesicles, and to date, CERK is the only identified mammalian enzyme known to produce C1P in cells. C1P has steadily emerged as a bioactive sphingolipid involved in cell proliferation, macrophage migration, and inflammatory events. The recent generation of the CERK knockout mouse and the development of CERK inhibitors have furthered our current understanding of CERK-derived C1P in regulating biological processes. In this chapter, the history of C1P as well as the biological functions attributed to C1P are reviewed. Keywords Ceramide kinase • Ceramide-1-phosphate • Eicosanoids • Proliferation • Immunity
L.A. Hoeferlin • D.S. Wijesinghe • C.E. Chalfant (*) Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, 1101 East Marshall Street, P.O. Box 980614, Richmond, VA 23298-0614, USA e-mail: [email protected] E. Gulbins and I. Petrache (eds.), Sphingolipids: Basic Science and Drug Development, Handbook of Experimental Pharmacology 215, DOI 10.1007/978-3-7091-1368-4_8, # Springer-Verlag Wien 2013
153
154
L.A. Hoeferlin et al.
1 Ceramide-1-Phosphate: The Early Years Ceramide-1-phosphate (C1P) is synthesized in mammalian cells by the direct phosphorylation of ceramide by ceramide kinase (CERK). To date, CERK is the only known mammalian enzyme to produce C1P (Sugiura et al. 2002), and the enzyme was first described by Bajjalieh and coworkers (1989) as a calciumstimulated lipid kinase co-purified with brain synaptic vesicles and possessing activity specific for the conversion of ceramide to C1P. Soon after this initial finding, the production of C1P was observed in the human pro-myelocytic leukemia cell line, HL-60 (Dressler and Kolesnick 1990). In this same study, the authors demonstrated that during stimulation, C1P was produced from ceramide derived from sphingomyelin, but not from glycosphingolipids. Follow-up studies by Kolesnick and Hemer (1990) reported a CERK activity distinguishable from diacylglycerol kinase in HL-60 cells verifying the findings of Bajjalieh and coworkers. After these initial studies, over a decade passed before successful cloning of the CERK enzyme was accomplished, and this new molecular “tool” provided researchers
Data Loading...
