| http://purl.uniprot.org/citations/2567291 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/2567291 | http://www.w3.org/2000/01/rdf-schema#comment | "The S-type alpha 1-antitrypsin (alpha 1AT) deficiency allele differs from the normal M1(Val213) allele by a single amino acid substitution (Glu264----Val). To evaluate the molecular pathophysiology responsible for the reduced serum levels of alpha 1AT associated with the S-type allele, alpha 1AT gene expression was examined in blood monocytes, cells which normally produce alpha 1AT, as well as murine fibroblasts modified by retroviral gene transfer to express the S-type and normal M-type human alpha 1AT genes. Northern analysis and S1 protection analysis demonstrated that monocytes of M and S homozygotes both express 1.8-kilobase alpha 1AT mRNA transcripts in comparable levels and similar in structure. Pulse-chase labeling studies demonstrated that both M and S monocytes synthesized and secreted a 52-kDa protein, but the S monocytes secreted significantly less. The cellular lysates of both M and S monocytes contained a newly synthesized 50-kDa precursor form of alpha 1AT, but the S monocytes contained reduced amounts. Pulse-chase labeling in the presence of tunicamycin, an inhibitor of core oligosaccharide addition, demonstrated that S monocytes exhibited a selective inhibition of secretion of 45-kDa nonglycosylated alpha 1AT not observed in M monocytes. Consistent with these observations, murine fibroblasts modified by retroviral gene transfer to contain an integrated human S-type alpha 1AT cDNA demonstrated reduced secretion of alpha 1AT compared with fibroblasts containing an integrated human M-type alpha 1AT cDNA and also reproduced the abnormality of alpha 1AT biosynthesis observed with S-type monocytes. Furthermore, in the presence of leupeptin, an inhibitor of cellular proteinases, the S-type modified fibroblasts demonstrated a selective augmentation of human alpha 1AT secretion not observed for the M-type. Together, these observations are consistent with the concept that the single A----T mutation of the S-type alpha 1AT gene results in reduced cellular secretion of alpha 1AT because the newly synthesized S-type alpha 1AT protein is degraded intracellularly prior to secretion."xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.org/dc/terms/identifier | "doi:10.1016/s0021-9258(18)81646-5"xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/author | "Curiel D.T."xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/author | "Courtney M."xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/author | "Crystal R.G."xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/author | "Chytil A."xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/date | "1989"xsd:gYear |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/pages | "10477-10486"xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/title | "Serum alpha 1-antitrypsin deficiency associated with the common S-type (Glu264----Val) mutation results from intracellular degradation of alpha 1-antitrypsin prior to secretion."xsd:string |
| http://purl.uniprot.org/citations/2567291 | http://purl.uniprot.org/core/volume | "264"xsd:string |
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