DESCRIBE <http://purl.uniprot.org/citations/9660788>

Subject	Predicate	Object
http://purl.uniprot.org/citations/9660788	http://www.w3.org/1999/02/22-rdf-syntax-ns#type	http://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9660788	http://www.w3.org/1999/02/22-rdf-syntax-ns#type	http://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9660788	http://www.w3.org/2000/01/rdf-schema#comment	"The acid sphingomyelinase (ASM) gene, which has been implicated in ceramide-mediated cell signaling and atherogenesis, gives rise to both lysosomal SMase (L-SMase), which is reportedly cation-independent, and secretory SMase (S-SMase), which is fully or partially dependent on Zn2+ for enzymatic activity. Herein we present evidence for a model to explain how a single mRNA gives rise to two forms of SMase with different cellular trafficking and apparent differences in Zn2+ dependence. First, we show that both S-SMase and L-SMase, which contain several highly conserved zinc-binding motifs, are directly activated by zinc. In addition, SMase assayed from a lysosome-rich fraction of Chinese hamster ovary cells was found to be partially zinc-dependent, suggesting that intact lysosomes from these cells contain subsaturating levels of Zn2+. Analysis of Asn-linked oligosaccharides and of N-terminal amino acid sequence indicated that S-SMase arises by trafficking through the Golgi secretory pathway, not by cellular release of L-SMase during trafficking to lysosomes or after delivery to lysosomes. Most importantly, when Zn2+-dependent S-SMase was incubated with SMase-negative cells, the enzyme was internalized, trafficked to lysosomes, and became zinc-independent. We conclude that L-SMase is exposed to cellular Zn2+ during trafficking to lysosomes, in lysosomes, and/or during cell homogenization. In contrast, the pathway targeting S-SMase to secretion appears to be relatively sequestered from cellular pools of Zn2+; thus S-SMase requires exogeneous Zn2+ for full activity. This model provides important information for understanding the enzymology and regulation of L- and S-SMase and for exploring possible roles of ASM gene products in cell signaling and atherogenesis."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.org/dc/terms/identifier	"doi:10.1074/jbc.273.29.18250"xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.org/dc/terms/identifier	"doi:10.1074/jbc.273.29.18250"xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Williams K.J."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Williams K.J."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Schuchman E.H."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Schuchman E.H."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Keesler G.A."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Keesler G.A."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Schissel S.L."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Schissel S.L."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Tabas I."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/author	"Tabas I."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/date	"1998"xsd:gYear
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/date	"1998"xsd:gYear
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/name	"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/name	"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/pages	"18250-18259"xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/pages	"18250-18259"xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/title	"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/title	"The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene."xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/volume	"273"xsd:string
http://purl.uniprot.org/citations/9660788	http://purl.uniprot.org/core/volume	"273"xsd:string