Metabolism of sphingomyelin by the sphingomyelinase, ceramidase (Cer'ase) and the sphingosine kinase (SK) enzymes results in formation of S1P and receptor activation. Autocrine and paracrine modes of receptor activation have been implied but have yet to be rigorously proven. Critical signaling molecules, such as phospholipase C (PLC), ERK, PI3K, and Akt are activated. Active Akt binds to the receptor and phosphorylates the third intracellular loop, which is essential for Rac activation. Representation of Figure 2. from T. Hla, et al. 2001, Science, 294, pg. 1877.
Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP26 CPTAC Assay Portal]a60G protein mediated signaling pathwayPW:0000125Pathway Ontologysphingosine 1-phosphate signaling pathwayPW:0000960Pathway Ontology11729304PubMedLysophospholipids--receptor revelations.Science2001Hla TLee MJAncellin NPaik JHKluk MJsignaling pathwayPW:0000003Pathway Ontology