Find SPHK1 Products Interaction Network for SPHK1 SPHK1 Details

Related Pathways Sphingolipid Metabolism Phospholipid Degradation PDGF Signaling View All Pathways

Synonyms: 1110006G24Rik, HSK, SK1, Sphingosine kinase, SPHK, SPHK1, SPHK1A

S-1P Stimulated Signaling

Sphingosine-1-phosphate (SPP/S-1P/S1P) is a bioactive sphingolipid generated within cells by types 1 and 2 sphingosine kinases (SPHK1, SPHK2). A variety of growth and survival factors enhance the expression and activation of SPHK1/2. The cytoplasmic enzyme, SPHK1, is recruited by ligand-activated platelet derived growth factor receptors (PDGF-R) where it locally enhances the conversion of sphingosine (Sph) to S-1P. Sphingosine and its precursor, ceramide (N-acylsphingosine) (Cer) are pro-apoptotic second messengers, whereas S-1P is anti-apoptotic. The conversion of Cer and Sph into S-1P shifts the ratio of pro-apoptotic to anti-apoptotic sphingolipids towards survival. The balance of the relative amounts of these phospholipids is referred to as the “sphingolipid rheostat”

Sphingosine-1-phosphate is linked to a variety of biological processes that affect cell growth, survival and motility. S-1P signaling involves two independent, but coordinated, mechanisms. S-1P regulates cell functions such as vascular maturation, angiogenesis, growth, survival, cytoskeletal organization and motility as an “inside out” agonist to a family of G-protein coupled receptors (GPCR). In addition, S-1P regulates cell growth, survival and calcium homeostasis as a GPCR receptor-independent “second messenger.

Secreted S-1P is known to bind to five differentially expressed members of the EDG-family of GPCR receptors: EDG-1/S1P1, EDG-5/S1P2, EDG-3/S1P3, EDG-6/S1P4, and EDG-8/S1P5/NRG-1. These receptors mediate their actions primarily through G-protein alpha i/o and alpha 12/13 subunits. These receptors are linked to angiogenesis, vascular maturation, neuronal survival and immunity especially as they affect aspects of cell migration, and chemotaxis. Second messenger (internal) S-1P stimulates cell growth, suppresses apoptosis and caspase activation by a variety of mechanisms. Sph-1-P blocks apoptosis, at least in part, by inhibiting the formation of ceramide from sphingomyelin by acidic sphingomyleinase.