Reactome | SPHK1 phosphorylates sphingoid

SPHK1 phosphorylates sphingoid

Stable Identifier

R-HSA-428273

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

ReviewStatus

5/5

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The cytosolic enzyme sphingosine kinase 1 (SPHK1) catalyzes the phosphorylation of sphingoids (SPG) to sphingoid 1-phosphate (S1P). The main product is sphingosine 1-phoshate, a bioactive lipid that acts extracellularly on G protein-coupled receptors of the S1P1/EDG-1 subfamily (Nava et al., 2000; Pitson et al., 2000; Wang et al., 2013; reviewed by Siow & Wattenberg, 2011). The isoforms SK1a, SK1b, and SK1c are produced through alternative splicing and show functional differences in their activity (reviewed by Hatoum et al., 2017). SPHK1 is regulated transcriptionally by transcription factors, cytokines, and micro-RNAs (reviewed by Bonica et al., 2020). Its activity is also modulated by posttranslational modifications and interactions with other proteins (reviewed by Pulkoski-Gross & Obeid, 2018). Through its product S1P, which is a multifunctional signaling lipid, SPHK1 is essential in inflammation processes (reviewed by Rauch, 2014). SPHK1 was also shown to be associated with cancer genesis, progression, and metastasic processes (Zhang et al., 2014).

Literature References

PubMed ID	Title	Journal	Year
21864225	The compartmentalization and translocation of the sphingosine kinases: mechanisms and functions in cell signaling and sphingolipid metabolism Siow, D, Wattenberg, B	Crit Rev Biochem Mol Biol	2011
10947957	Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes D'Andrea, RJ, Pitson, SM, Gamble, JR, Vadas, MA, Wattenberg, BW, Moretti, PA, Vandeleur, L, Xia, P	Biochem J	2000
33171624	Transcriptional Regulation of Sphingosine Kinase 1 Mao, C, Bonica, J, Hannun, YA, Obeid, LM	Cells	2020
30591148	Molecular mechanisms of regulation of sphingosine kinase 1 Pulkoski-Gross, MJ, Obeid, LM	Biochim Biophys Acta Mol Cell Biol Lipids	2018
24977491	Sphingosine 1-phosphate as a link between blood coagulation and inflammation Rauch, BH	Cell Physiol Biochem	2014
23602659	Molecular basis of sphingosine kinase 1 substrate recognition and catalysis Romanow, W, Walker, N, Dai, J, Xiao, SH, Johnstone, S, Thibault, S, An, S, Xu, H, Meininger, D, Min, X, Liu, J, Wang, Z	Structure	2013
28415564	Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget Hatoum, D, McGowan, EM, Nassif, NT, Lin, Y, Haddadi, N	Oncotarget	2017
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