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 This pathway was inferred from Homo sapiens pathway [http://wikipathways.org/instance/WP26_r79950 WP26 (r79950)] with a 100.0% conversion rate. a60 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:8877 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:56848 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:427 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6610 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1901 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:9294 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:1903 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:53637 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:23236 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5330 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5331 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5595 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5594 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5597 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5596 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5598 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:6300 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2770 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2771 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:2773 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:207 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:208 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:10000 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:5287 Homology Mapping from Homo sapiens to Rattus norvegicus: Original ID = L:29127 G protein mediated signaling pathway PW:0000125 Pathway Ontology sphingosine 1-phosphate signaling pathway PW:0000960 Pathway Ontology 11729304 PubMed Lysophospholipids--receptor revelations. Science 2001 Hla T Lee MJ Ancellin N Paik JH Kluk MJ