Reactome | p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate

p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate

Stable Identifier

R-HSA-5218845

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

ReviewStatus

5/5

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p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate

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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).

Literature References

PubMed ID	Title	Journal	Year
10802064	Functional characterization of human sphingosine kinase-1 Nava, VE, Lacana, E, Poulton, S, Liu, H, Sugiura, M, Kono, K, Milstien, S, Kohama, T, Spiegel, S	FEBS Lett	2000
12391145	Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases Shu, X, Wu, W, Mosteller, RD, Broek, D	Mol. Cell. Biol.	2002
12776187	VEGF receptor expression and signaling in human bladder tumors Wu, W, Shu, X, Hovsepyan, H, Mosteller, RD, Broek, D	Oncogene	2003