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Sphingosine Kinase Type 2 Is a Putative BH3-only Protein That Induces Apoptosis
Open accessAbstract
There are two isoforms of sphingosine kinase (SphK) that catalyze the formation of sphingosine 1-phosphate, a potent sphingolipid mediator. Whereas SphK1 stimulates growth and survival, here we show that SphK2 enhanced apoptosis in diverse cell types and also suppressed cellular proliferation. Apoptosis was preceded by cytochrome c release and activation of caspase-3. SphK2-induced apoptosis was independent of activation of sphingosine 1-phosphate receptors. Sequence analysis revealed that SphK2 contains a 9-amino acid motif similar to that present in BH3-only proteins, a pro-apoptotic subgroup of the Bcl-2 family. As with other BH3-only proteins, co-immunoprecipitation demonstrated that SphK2 interacted with Bcl-xL. Moreover, site-directed mutation of Leu-219, the conserved leucine residue present in all BH3 domains, markedly suppressed SphK2-induced apoptosis. Hence, the apoptotic effect of SphK2 might be because of its putative BH3 domain.
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Letai, A., Bassik, M. C., Walensky, L. D., Sorcinelli, M. D., Weiler, S., & Korsmeyer, S. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00127-7 · Cited by 1,677
Puthalakath, H., Villunger, A., O'Reilly, L. A., Beaumont, J. G., Coultas, L., Cheney, R. E., Huang, D. C. S., & Strasser, A. (2001) · Science · doi:10.1126/science.1062257 · Cited by 656
Cited by
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Pyne, N. J., & Pyne, S. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2875 · Cited by 852
BH3-only proteins in apoptosis and beyond: an overview
Lomonosova, E., & Chinnadurai, G. (2008) · Oncogene · doi:10.1038/onc.2009.39 · Cited by 458
Lysophospholipid receptors: Signalling, pharmacology and regulation by lysophospholipid metabolism
Meyer zu Heringdorf, D., & Jakobs, K. H. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.09.026 · Cited by 388
An update on sphingosine-1-phosphate and other sphingolipid mediators
Fyrst, H., & Saba, J. D. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.392 · Cited by 344
Sphingolipids: regulators of crosstalk between apoptosis and autophagy
Young, M. M., Kester, M., & Wang, H.-G. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r031278 · Cited by 329
Metadata
- Authors
- Liu, H., Toman, R. E., Goparaju, S. K., Maceyka, M., Nava, V. E., Sankala, H., Payne, S. G., Bektas, M., Ishii, I., Chun, J., Milstien, S., & Spiegel, S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 278
- Issue
- 41
- Pages
- 40330-40336
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2110388058
- Cited by
- 356
- References
- 2
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Liu, H., Toman, R. E., Goparaju, S. K., Maceyka, M., Nava, V. E., Sankala, H., Payne, S. G., Bektas, M., Ishii, I., Chun, J., Milstien, S., & Spiegel, S. (2003). Sphingosine Kinase Type 2 Is a Putative BH3-only Protein That Induces Apoptosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m304455200
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