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. 1877This pathway was inferred from Homo sapiens pathway [http://wikipathways.org/instance/WP26_r79950 WP26 (r79950)] with a 100.0% conversion rate.a60Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8877Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:56848Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:427Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6610Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1901Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9294Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1903Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:53637Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:23236Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5330Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5331Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5595Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5594Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5597Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5596Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5598Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6300Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2770Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2771Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2773Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:207Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:208Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:10000Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5287Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:29127G protein mediated signaling pathwayPW:0000125Pathway Ontologysphingosine 1-phosphate signaling pathwayPW:0000960Pathway Ontology11729304PubMedLysophospholipids--receptor revelations.Science2001Hla TLee MJAncellin NPaik JHKluk MJ