p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate

Stable Identifier
Homo sapiens
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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

Sugiura, M, Poulton, S, Liu, H, Nava, VE, Spiegel, S, Kohama, T, Milstien, S, Kono, K, Lacana, E

FEBS Lett 2000
12391145 Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases

Wu, W, Mosteller, RD, Shu, X, Broek, D

Mol. Cell. Biol. 2002
12776187 VEGF receptor expression and signaling in human bladder tumors

Wu, W, Mosteller, RD, Shu, X, Hovsepyan, H, Broek, D

Oncogene 2003
Catalyst Activity

D-erythro-sphingosine kinase activity of p-S225-SPHK1 [cytosol]

Orthologous Events
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