The extended family of neutral sphingomyelinases.
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.
Clarke
Christopher J
CJ
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Snook
Christopher F
CF
Tani
Motohiro
M
Matmati
Nabil
N
Marchesini
Norma
N
Hannun
Yusuf A
YA
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
D013108:Sphingomyelin Phosphodiesterase