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Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate.
J Biol Chem 2008; 283(9):5677-84JB

Abstract

Ceramide is an important lipid signaling molecule and a key intermediate in sphingolipid biosynthesis. Recent studies have implied a previously unappreciated role for the ceramide N-acyl chain length, inasmuch as ceramides containing specific fatty acids appear to play defined roles in cell physiology. The discovery of a family of mammalian ceramide synthases (CerS), each of which utilizes a restricted subset of acyl-CoAs for ceramide synthesis, strengthens this notion. We now report the characterization of mammalian CerS2. qPCR analysis reveals that CerS2 mRNA is found at the highest level of all CerS and has the broadest tissue distribution. CerS2 has a remarkable acyl-CoA specificity, showing no activity using C16:0-CoA and very low activity using C18:0, rather utilizing longer acyl-chain CoAs (C20-C26) for ceramide synthesis. There is a good correlation between CerS2 mRNA levels and levels of ceramide and sphingomyelin containing long acyl chains, at least in tissues where CerS2 mRNA is expressed at high levels. Interestingly, the activity of CerS2 can be regulated by another bioactive sphingolipid, sphingosine 1-phosphate (S1P), via interaction of S1P with two residues that are part of an S1P receptor-like motif found only in CerS2. These findings provide insight into the biochemical basis for the ceramide N-acyl chain composition of cells, and also reveal a novel and potentially important interplay between two bioactive sphingolipids that could be relevant to the regulation of sphingolipid metabolism and the opposing functions that these lipids play in signaling pathways.

Authors+Show Affiliations

Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18165233

Citation

Laviad, Elad L., et al. "Characterization of Ceramide Synthase 2: Tissue Distribution, Substrate Specificity, and Inhibition By Sphingosine 1-phosphate." The Journal of Biological Chemistry, vol. 283, no. 9, 2008, pp. 5677-84.
Laviad EL, Albee L, Pankova-Kholmyansky I, et al. Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. J Biol Chem. 2008;283(9):5677-84.
Laviad, E. L., Albee, L., Pankova-Kholmyansky, I., Epstein, S., Park, H., Merrill, A. H., & Futerman, A. H. (2008). Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. The Journal of Biological Chemistry, 283(9), pp. 5677-84. doi:10.1074/jbc.M707386200.
Laviad EL, et al. Characterization of Ceramide Synthase 2: Tissue Distribution, Substrate Specificity, and Inhibition By Sphingosine 1-phosphate. J Biol Chem. 2008 Feb 29;283(9):5677-84. PubMed PMID: 18165233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. AU - Laviad,Elad L, AU - Albee,Lee, AU - Pankova-Kholmyansky,Irene, AU - Epstein,Sharon, AU - Park,Hyejung, AU - Merrill,Alfred H,Jr AU - Futerman,Anthony H, Y1 - 2007/12/28/ PY - 2008/1/1/pubmed PY - 2008/4/16/medline PY - 2008/1/1/entrez SP - 5677 EP - 84 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 283 IS - 9 N2 - Ceramide is an important lipid signaling molecule and a key intermediate in sphingolipid biosynthesis. Recent studies have implied a previously unappreciated role for the ceramide N-acyl chain length, inasmuch as ceramides containing specific fatty acids appear to play defined roles in cell physiology. The discovery of a family of mammalian ceramide synthases (CerS), each of which utilizes a restricted subset of acyl-CoAs for ceramide synthesis, strengthens this notion. We now report the characterization of mammalian CerS2. qPCR analysis reveals that CerS2 mRNA is found at the highest level of all CerS and has the broadest tissue distribution. CerS2 has a remarkable acyl-CoA specificity, showing no activity using C16:0-CoA and very low activity using C18:0, rather utilizing longer acyl-chain CoAs (C20-C26) for ceramide synthesis. There is a good correlation between CerS2 mRNA levels and levels of ceramide and sphingomyelin containing long acyl chains, at least in tissues where CerS2 mRNA is expressed at high levels. Interestingly, the activity of CerS2 can be regulated by another bioactive sphingolipid, sphingosine 1-phosphate (S1P), via interaction of S1P with two residues that are part of an S1P receptor-like motif found only in CerS2. These findings provide insight into the biochemical basis for the ceramide N-acyl chain composition of cells, and also reveal a novel and potentially important interplay between two bioactive sphingolipids that could be relevant to the regulation of sphingolipid metabolism and the opposing functions that these lipids play in signaling pathways. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/18165233/Characterization_of_ceramide_synthase_2:_tissue_distribution_substrate_specificity_and_inhibition_by_sphingosine_1_phosphate_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=18165233 DB - PRIME DP - Unbound Medicine ER -