SPHK2 explained

Sphingosine kinase 2 is a protein that in humans is encoded by the SPHK2 gene.^[1]

This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.^{[1] [2]}

The researchers also found that the expression of sphingosine kinase 2 (SphK2) and the secretion of sphingosine-1-phosphate (S1P) were significantly upregulated in the lungs of CS-exposed mice with COPD-like symptoms.^[3]

Inhibitors

• Opaganib

Further reading

• Liu H, Sugiura M, Nava VE, Edsall LC, Kono K, Poulton S, Milstien S, Kohama T, Spiegel S . Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform . The Journal of Biological Chemistry . 275 . 26 . 19513–20 . June 2000 . 10751414 . 10.1074/jbc.M002759200 . free .
• Xia P, Wang L, Moretti PA, Albanese N, Chai F, Pitson SM, D'Andrea RJ, Gamble JR, Vadas MA . Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling . The Journal of Biological Chemistry . 277 . 10 . 7996–8003 . March 2002 . 11777919 . 10.1074/jbc.M111423200 . free .
• Shu X, Wu W, Mosteller RD, Broek D . Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases . Molecular and Cellular Biology . 22 . 22 . 7758–68 . November 2002 . 12391145 . 134718 . 10.1128/mcb.22.22.7758-7768.2002 .
• Paugh SW, Payne SG, Barbour SE, Milstien S, Spiegel S . The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2 . FEBS Letters . 554 . 1–2 . 189–93 . November 2003 . 14596938 . 10.1016/S0014-5793(03)01168-2 . 41465940 . free .
• Hait NC, Sarkar S, Le Stunff H, Mikami A, Maceyka M, Milstien S, Spiegel S . Role of sphingosine kinase 2 in cell migration toward epidermal growth factor . The Journal of Biological Chemistry . 280 . 33 . 29462–9 . August 2005 . 15951439 . 10.1074/jbc.M502922200 . free .
• Okada T, Ding G, Sonoda H, Kajimoto T, Haga Y, Khosrowbeygi A, Gao S, Miwa N, Jahangeer S, Nakamura S . Involvement of N-terminal-extended form of sphingosine kinase 2 in serum-dependent regulation of cell proliferation and apoptosis . The Journal of Biological Chemistry . 280 . 43 . 36318–25 . October 2005 . 16103110 . 10.1074/jbc.M504507200 . free .
• Olivera A, Urtz N, Mizugishi K, Yamashita Y, Gilfillan AM, Furumoto Y, Gu H, Proia RL, Baumruker T, Rivera J . IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and contributes to mast cell responses . The Journal of Biological Chemistry . 281 . 5 . 2515–25 . February 2006 . 16316995 . 10.1074/jbc.M508931200 . free .
• Sun J, Yan G, Ren A, You B, Liao JK . FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1 . Circulation Research . 99 . 5 . 468–76 . September 2006 . 16888242 . 2614439 . 10.1161/01.RES.0000239410.65551.b3 .
• Hait NC, Bellamy A, Milstien S, Kordula T, Spiegel S . Sphingosine kinase type 2 activation by ERK-mediated phosphorylation . The Journal of Biological Chemistry . 282 . 16 . 12058–65 . April 2007 . 17311928 . 10.1074/jbc.M609559200 . free .
• Ding G, Sonoda H, Yu H, Kajimoto T, Goparaju SK, Jahangeer S, Okada T, Nakamura S . Protein kinase D-mediated phosphorylation and nuclear export of sphingosine kinase 2 . The Journal of Biological Chemistry . 282 . 37 . 27493–502 . September 2007 . 17635916 . 10.1074/jbc.M701641200 . free .

Notes and References

1. Web site: Entrez Gene: Sphingosine kinase 2. 2011-12-22 .
2. provided by RefSeq, Aug 2011
3. Chen . Yanhui . Zhang . Yongrong . Rao . Cheng . Huang . Jieyun . Qing . Qiong . 2023-03-16 . Deletion of sphingosine kinase 2 attenuates cigarette smoke-mediated chronic obstructive pulmonary disease-like symptoms by reducing lung inflammation . Biomolecules and Biomedicine . en . 23 . 2 . 259–270 . 10.17305/bjbms.2022.8034 . 36226596 . 2831-090X. 10113950 .