title: Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis.
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 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.
authors.affiliation: Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0614, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Rachelle E
authors.initials: RE
authors.lastname: Toman
authors.forename: Sravan K
authors.initials: SK
authors.lastname: Goparaju
authors.forename: Michael
authors.initials: M
authors.lastname: Maceyka
authors.forename: Victor E
authors.initials: VE
authors.lastname: Nava
authors.forename: Heidi
authors.initials: H
authors.lastname: Sankala
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Payne
authors.forename: Meryem
authors.initials: M
authors.lastname: Bektas
authors.forename: Isao
authors.initials: I
authors.lastname: Ishii
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Sheldon
authors.initials: S
authors.lastname: Milstien
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiegel
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099157:Sphingosine Kinase
chemical_list: D018076:DNA, Complementary; D007527:Isoenzymes; D010446:Peptide Fragments; D017853:Phosphotransferases (Alcohol Group Acceptor); D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D000099157:Sphingosine Kinase; C474007:Bax protein (53-86)