title: The extended family of neutral sphingomyelinases.
abstract: The neutral sphingomyelinases (N-SMases) are considered major candidates for mediating the stress-induced production of ceramide, and N-SMase activity has been identified, characterized, and cloned from bacteria, yeast, and mammalian cells. Although the level of identity between these enzymes is low, a number of key residues thought to be involved in metal binding and catalysis are conserved. This has led to the suggestion of a common catalytic mechanism, and thus, these enzymes are considered to form an extended family of N-SMases. Despite considerable research into N-SMase activity in cell culture and various tissues, the lack, until recently, of molecular identification of specific N-SMase enzymes had precluded specific insights into the regulation, physiological, and pathological roles of these proteins. In this review, we summarize, for the first time, current knowledge of the N-SMase family, focusing on cloned members from bacteria, yeast, and mammalian cells. We also briefly consider the major future directions for N-SMase research which promises highly significant and specific insight into sphingolipid-mediated functions.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Clarke
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Snook
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tani
authors.forename: Nabil
authors.initials: N
authors.lastname: Matmati
authors.forename: Norma
authors.initials: N
authors.lastname: Marchesini
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry / Q000378:metabolism*; D015003:Yeasts / Q000201:enzymology
chemical_list: D013108:Sphingomyelin Phosphodiesterase