S1P receptor signal transduction (WP1312)

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.
last edited


MaintBot, Ddigles, Mkutmon, and Eweitz

Cited In


Rattus norvegicus



Pathway Ontology: G protein mediated signaling pathway sphingosine 1-phosphate signaling pathway


Label Type Compact Identifier
Plcb2 GeneProduct ensembl:ENSRNOG00000058337
Mapk1 GeneProduct ensembl:ENSRNOG00000001849
Gnai3 GeneProduct ensembl:ENSRNOG00000019465
S1pr5 GeneProduct ensembl:ENSRNOG00000020901
Smpd2 GeneProduct ensembl:ENSRNOG00000000306
Asah1 GeneProduct ensembl:ENSRNOG00000010034
Sphk2 GeneProduct ensembl:ENSRNOG00000021032
Akt1 GeneProduct ensembl:ENSRNOG00000028629
LOC100912585 GeneProduct ensembl:ENSRNOG00000002412
Mapk3 GeneProduct ensembl:ENSRNOG00000053583
S1pr2 GeneProduct ensembl:ENSRNOG00000020653
Sphk1 GeneProduct ensembl:ENSRNOG00000010626
S1pr1 GeneProduct ensembl:ENSRNOG00000013683
Gnai2 GeneProduct ensembl:ENSRNOG00000016592
Mapk6 GeneProduct ensembl:ENSRNOG00000009381
Pik3c2b GeneProduct ensembl:ENSRNOG00000029938
Plcb1 GeneProduct ensembl:ENSRNOG00000004810
Racgap1 GeneProduct ensembl:ENSRNOG00000049033
Mapk4 GeneProduct ensembl:ENSRNOG00000015401
Plcb3 GeneProduct ensembl:ENSRNOG00000021150
S1pr3 GeneProduct ensembl:ENSRNOG00000014524
Gnai1 GeneProduct ensembl:ENSRNOG00000057096
Mapk12 GeneProduct ensembl:ENSRNOG00000031233
Akt3 GeneProduct ensembl:ENSRNOG00000021497
Akt2 GeneProduct ensembl:ENSRNOG00000018677


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