S1P receptor signal transduction (WP26)

Homo sapiens

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]


Scott Doniger , Thomas Kelder , Martijn Van Iersel , Kristina Hanspers , Alex Pico , Daniela Digles , Zahra Roudbari , Eric Weitz , Denise Slenter , and Egon Willighagen


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Homo sapiens



Pathway Ontology

G protein mediated signaling pathway sphingosine 1-phosphate signaling pathway signaling pathway


Label Type Compact URI Comment
PLCB2 GeneProduct ncbigene:5330
MAPK1 GeneProduct ncbigene:5594
GNAI3 GeneProduct ncbigene:2773
EDG8 GeneProduct ncbigene:53637
SMPD2 GeneProduct ncbigene:6610
ASAH1 GeneProduct ncbigene:427
SPHK2 GeneProduct ncbigene:56848
AKT1 GeneProduct ncbigene:207
MAPK7 GeneProduct ncbigene:5598
MAPK3 GeneProduct ncbigene:5595
EDG5 GeneProduct ncbigene:9294
SPHK1 GeneProduct ncbigene:8877
S1PR1 GeneProduct ncbigene:1901
GNAI2 GeneProduct ncbigene:2771
MAPK6 GeneProduct ncbigene:5597
PIK3C2B GeneProduct ncbigene:5287
PLCB1 GeneProduct ncbigene:23236
RACGAP1 GeneProduct ncbigene:29127
MAPK4 GeneProduct ncbigene:5596
PLCB3 GeneProduct ncbigene:5331
EDG3 GeneProduct ncbigene:1903
GNAI1 GeneProduct ncbigene:2770
MAPK12 GeneProduct ncbigene:6300
AKT3 GeneProduct ncbigene:10000
AKT2 GeneProduct ncbigene:208


  1. Lysophospholipids--receptor revelations. Hla T, Lee MJ, Ancellin N, Paik JH, Kluk MJ. Science. 2001 Nov 30;294(5548):1875–8. PubMed Europe PMC Scholia