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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Apoptosis
Proteins
Chemical activation
Lysosphingolipid Receptors
Amino Acid Motifs
Sphingolipids
Cytochromes c
Immunoprecipitation
Leucine
Caspase 3
Sequence Analysis
Protein Isoforms
Cell Proliferation
Amino Acids
Mutation
sphingosine kinase
Growth
sphingosine 1-phosphate

ASJC Scopus subject areas

  • Biochemistry

Cite this

Liu, H., Toman, R. E., Goparaju, S. K., Maceyka, M., Nava, V. E., Sankala, H., ... 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

Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. / Liu, Hong; Toman, Rachelle E.; Goparaju, Sravan K.; Maceyka, Michael; Nava, Victor E.; Sankala, Heidi; Payner, Shawn G.; Bektas, Meryem; Ishii, Isao; Chun, Jerold; Milstien, Sheldon; Spiegel, Sarah.

In: Journal of Biological Chemistry, Vol. 278, No. 41, 10.10.2003, p. 40330-40336.

Research output: Contribution to journalArticle

Liu, H, Toman, RE, Goparaju, SK, Maceyka, M, Nava, VE, Sankala, H, Payner, SG, 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, vol. 278, no. 41, pp. 40330-40336. https://doi.org/10.1074/jbc.M304455200
Liu H, Toman RE, Goparaju SK, Maceyka M, Nava VE, Sankala H et al. Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. Journal of Biological Chemistry. 2003 Oct 10;278(41):40330-40336. https://doi.org/10.1074/jbc.M304455200
Liu, Hong ; Toman, Rachelle E. ; Goparaju, Sravan K. ; Maceyka, Michael ; Nava, Victor E. ; Sankala, Heidi ; Payner, Shawn G. ; Bektas, Meryem ; Ishii, Isao ; Chun, Jerold ; Milstien, Sheldon ; Spiegel, Sarah. / Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 41. pp. 40330-40336.
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