Sphingosine Kinase 2 Monoclonal Antibody (Clone 2C6)

Sphingosine kinase 2 (SPHK2) is an ATP-dependent lipid kinase that is encoded by the SPHK2 gene in humans.¹ It is composed of an N-terminal domain that contains an ATP binding site and a C-terminal domain that mediates substrate binding and specificity. SPHK2 is localized to the mitochondria, nucleus, and endoplasmic reticulum and is expressed in a wide variety of tissues, including the liver and kidney.² Upon cellular stimulation with EGF, phorbol 12-myristate 13-acetate (PMA; Item No. 10008014), or FcεRI, SPHK2 is activated and catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P).^3,1 SPHK2 has roles in many physiological and pathological processes, including cancer, inflammation, and neurodegenerative diseases.^1,4,5,6,7 Unlike SPHK1, SPHK2-derived S1P increases apoptosis and inhibits cell growth in vitro.^8,9,10 In vivo, hepatic SPHK2 regenerates S1P intracellularly after its dephosphorylation to sphingosine by the phospholipid phosphatase LPP3 at the cell membrane, which removes a portion of the sphingosine from the circulation. Therefore, inhibition of SPHK2 results in a paradoxical increase in circulating S1P levels as sphingosine returns to the circulation where it can be phosphorylated by SPHK1.¹¹ Overexpression of SPHK2 increases intracellular calcium levels and induces apoptosis in NIH3T3 cancer cells and reduces LPS-induced increases in TNF-α and IL-6 levels in isolated human peripheral blood mononuclear cell-derived macrophages in vitro.^4,5 SPHK2 activity is increased in postmortem frontal cortex from patients with Alzheimer's disease.⁷ Cayman’s Sphingosine Kinase 2 Monoclonal Antibody (Clone 2C6) can be used for ELISA and Western blot (WB) applications. The antibody recognizes SPHK2 at 69 kDa from human samples.

WARNING This product is not for human or veterinary use.

1. Hatoum, D., Haddadi, N., Lin, Y., et al. Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: Challenges for SphK as an oncotarget. Oncotarget 8(22), 36898-36929 (2017).

2. Liu, H., Sugiura, M., Nava, V.E., et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. The Journal of Biological Chemisty 275(26), 19513-19520 (2000).

3. Hait, N.C., Bellamy, A., Milstien, S., et al. Sphingosine kinase type 2 activation by ERK-mediated phosphorylation. The Journal of Biological Chemisty 282(16), 12058-12065 (2007).

4. Maceyka, M., Sankala, H., Hait, N.C., et al. SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism. The Journal of Biological Chemisty 280(44), 37118-37129 (2005).

5. Weigert, A., von Knethen, A., Thomas, D., et al. Sphingosine kinase 2 is a negative regulator of inflammatory macrophage activation. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1864(9), 1235-1246 (2019).

6. Samy, E.T., Meyer, C.A., Caplazi, P., et al. Cutting edge: Modulation of intestinal autoimmunity and IL-2 signaling by sphingosine kinase 2 independent of sphingosine 1-phosphate. J. Immunol. 179(9), 5644-5648 (2007).

7. Takasugi, N., Sasaki, T., Suzuki, K., et al. BACE1 activity is modulated by cell-associated sphingosine-1-phosphate. J. Neurosci. 31(18), 6850-6857 (2011).

8. Liu, H., Toman, R.E., Goparaju, S.K., et al. Sphingosine kinase type 2 is a putative BH₃-only protein that induces apoptosis. The Journal of Biological Chemisty 278(41), 40330-40336 (2003).

9. Maceyka, M., Milstien, S., and Spiegel, S. Sphingosine kinases, sphingosine-1-phosphate and sphingolipidomics. Prostaglandins Other Lipid Mediat. 77(1-4), 15-22 (2005).

10. Haddadi, N., Lin, Y., Simpson, A.M., et al. "Dicing and splicing" sphingosine kinase and relevance to cancer. Int. J. Mol. Sci. 18(9), 1891 (2017).

11. Kharel, Y., Huang, T., Salamon, A., et al. Mechanism of sphingosine 1-phosphate clearance from blood. Biochem. J. 477(5), 925-935 (2020).