| http://purl.uniprot.org/citations/22383528 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22383528 | http://www.w3.org/2000/01/rdf-schema#comment | "Fibroblasts from the fro/fro mouse, with a deletion in the Smpd3 gene coding for the active site of neutral sphingomyelinase 2 (NSMase2), secreted increased amounts of hyaluronan (HA). This was reversed by transfection with the Smpd3 gene, suggesting a connection between sphingolipid and glycosaminoglycan metabolism. The deficiency of NSMase2 resulted in storage of sphingomyelin (SM) and cholesterol with a 50% reduction in ceramides (Cer). RT-PCR and Western blot analysis showed that increased HA secretion resulted from increased hyaluronan synthase 2 (HAS2) activity localized to sphingolipid-enriched lipid rafts. Although cholesterol levels were also elevated in lipid rafts from mouse fibroblasts deficient in lysosomal acid SMase activity (deletion of the Smpd1(-/-) gene), there was no increase in HA secretion. We then showed that in fro/fro fibroblasts, the reduced ceramide was associated with decreased phosphorylation of protein phosphatase 2A (PP2A) and increased phosphorylation of its substrate Akt-p, together with PI3K, PDK1, mTOR (mammalian target of rapamycin), and p70S6K, although PTEN was unaffected. Exogenous ceramide, as well as inhibitors of Akt (Akt inhibitor VIII), PI 3-kinase (LY294002 and wortmannin), and mTOR (rapamycin) reduced secretion of HA, whereas the NSMase2 inhibitor GW4869 increased HA synthesis and secretion. We propose that NSMase2/Cer are the key mediators of the regulation of HA synthesis, via microdomains and the Akt/mTOR pathway."xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.304857"xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/author | "Qin J."xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/author | "Dawson G."xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/author | "Berdyshev E."xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/author | "Schwartz N.B."xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/author | "Poirer C."xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/pages | "13620-13632"xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/title | "Neutral sphingomyelinase 2 deficiency increases hyaluronan synthesis by up-regulation of Hyaluronan synthase 2 through decreased ceramide production and activation of Akt."xsd:string |
| http://purl.uniprot.org/citations/22383528 | http://purl.uniprot.org/core/volume | "287"xsd:string |
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