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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
1998-7-17
|
| pubmed:abstractText |
Production of endothelin (ET-1) is believed to be a three-step process, consisting of an initial proteolytic cleavage by signal peptidase of preproET-1, a second cleavage of proET-1 to big ET-1-Lys-Arg by dibasic amino acid-specific convertase and C-terminal trimming, and finally the processing of Big ET-1 to ET-1 by endothelin-converting enzyme (ECE). To clarify the relationships between the second processing step and the third, we introduced point mutation into ET-1 cDNA to replace the Arg in the -4 position of the recognition motifs of furin-like convertase in human preproET-1 (Arg49 or Arg89) by Gly. When mutant cDNAs were expressed in CHO-K1 cells, they failed to be processed at the mutated processing signal, suggesting the involvement of the enzyme with furin-like specificity in the processing at dibasic amino acid motifs. Co-transfection of mutant preproET-1 cDNA and ECE-1 cDNA revealed that cleavage at Arg92 is essential for cleavage by ECE-1 but that cleavage at Arg52 is not. Although without cleavage at Arg52 a high molecular weight form of ET-1, designated Large ET-1, is produced by processing by ECE-1, it did not evoke a Ca2+ transient in ETA receptor-expressing cells. In conclusion, the cleavage by furin-like convertase is essential for the production of active ET-1.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0160-2446
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
31 Suppl 1
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
S13-5
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading | |
| pubmed:year |
1998
|
| pubmed:articleTitle |
The processing pathway of endothelin-1 production.
|
| pubmed:affiliation |
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|