Reaction: p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate
- in pathway: VEGFR2 mediated cell proliferation
Membrane-bound sphingosine (SPG) in cells attenuates basal Ras activity by stimulating the activity of Ras GTPase-activating proteins (RasGAPs). Upon its phosphorylation by SPHK1, SPG is converted to sphingosine 1-phosphate (S1P) which then displaces from GAP downregulating RASA1 (p120GAP) activity and thereby induces Ras-GTP accumulation. This overall increases the level of activated Ras-GTP leading to activation of the ERK/mitogen-activated protein kinase (MAPK) pathway and cell division (Shu et al. 2002, Wu et al. 2003, Spiegel & Milstien 2006).
Reaction - small molecule participants:
S1P [plasma membrane]
ADP [cytosol]
ATP [cytosol]
Reactome.org reaction link: R-HSA-5218845
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Reaction input - small molecules:
ATP(4-)
Reaction output - small molecules:
sphingosine 1-phosphate(1-)
ADP(3-)
Reactome.org link: R-HSA-5218845