Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis

Hong Liu, Rachelle E. Toman, Sravan K. Goparaju, Michael Maceyka, Victor E. Nava, Heidi Sankala, Shawn G. Payner, Meryem Bektas, Isao Ishii, Jerold Chun, Sheldon Milstien, Sarah Spiegel

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275 Citations (Scopus)

Abstract

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 proapoptotic subgroup of the Bcl-2 family. As with other BH3-only proteins, co-immunoprecipitation demonstrated that SphK2 interacted with Bcl-x L. 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.

Original languageEnglish
Pages (from-to)40330-40336
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number41
DOIs
Publication statusPublished - 2003 Oct 10

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Liu, H., Toman, R. E., Goparaju, S. K., Maceyka, M., Nava, V. E., Sankala, H., Payner, 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, 278(41), 40330-40336. https://doi.org/10.1074/jbc.M304455200