Ceramide Kinase

Sphingolipids, in addition to being structural components of membranes, regulate cell-cell and cell-substrate interactions, proliferation, and differentiation. Members of this diverse group of lipids have emerged as a novel class of signaling molecules that also regulate phagocytosis. The mechanisms by which sphingolipids exert these effects remain incompletely defined. More than a decade ago, it was found that ceramide can be phosphorylated to ceramide 1-phosphate (C1P). Ceramide kinase (CERK) and its phosphorylated product ceramide 1-phosphate (C1P) are central players in inflammation and cancer. The product of CERK activity, ceramide 1-phosphate (C1P), has been reported to have mitogenic effects. C1P is a direct activator of cytosolic phospholipase A2 and is involved in arachidonic acid release. CERK is a mediator of Ca2+-dependent degranulation in mast cells. In both arachidonic acid release and mast cell degranulation, the intracellular elevation of Ca2+ is a central event that acts as a regulatory mechanism of CERK activity. C1P is found in brain synaptic vesicles, and plays a role in regulating the secretion of neurotransmitters. CERK activity exists in HL-60 cells where the C1P is derived from ceramide released from sphingomyelin. The expressed kinase has specific ceramide phosphorylating activity. CERKs exist in a variety of cellular organisms, including plants, nematodes, insects, and vertebrates.