Fig. 2: S1P functions through diverse signalling mechanisms.
From: Sphingosine 1-phosphate signalling in cancer stem cells
SPHK1 mediated S1P production is proposed to occur at the plasma membrane, where S1P is subsequently exported from the cell to function in an autocrine and paracrine fashion by binding S1PR1-5 and activating canonical G protein-mediated pathways. This receptor activation drives the Ras/extracellular signal-regulated kinase (ERK)1/2, phosphatidylinositol-3-kinase (PI3K)/Akt and phospholipase C (PLC) pathways to enhance cell proliferation and survival. G protein-mediated activation of Rac GTPase and Rho/Rho-associated protein kinase (ROCK) promotes cell migration, Intracellular S1P, often linked to generation by SPHK2, has numerous intracellular targets regulating diverse cellular functions including BAX (BCL2-associated X protein) mediated apoptosis, prohibitin 2 (PHB2) driven respiration, human telomerase reverse transcriptase (hTERT) mediated cell replication and inhibition of histone deacetylases 1 and 2 (HDAC1/2). Created in https://BioRender.com.
