A tissue-type plasminogen activator mutant with prolonged clearance in vivo. Effect of removal of the growth factor domain.
- Resource Type
- Article
- Authors
- Browne, M J; Carey, J E; Chapman, C G; Tyrrell, A W; Entwisle, C; Lawrence, G M; Reavy, B; Dodd, I; Esmail, A; Robinson, J H
- Source
- Journal of Biological Chemistry; February 1988, Vol. 263 Issue: 4 p1599-1602, 4p
- Subject
- Language
- ISSN
- 00219258; 1083351X
The complete cDNA for human tissue-type plasminogen activator (t-PA) was cloned and sequenced. A mutant was constructed by using in vitro site-specific mutagenesis to delete the region encoding the growth factor domain (amino acids 51-87 inclusive). Normal and mutant t-PA species were produced using two mammalian expression systems (in human HeLa cells and mouse C127 cells). The clearance of mutant and normal t-PA from plasma was examined in vivo using a guinea pig model. Mutant t-PA derived from HeLa or C127 cells was cleared much more slowly than the cognate normal t-PA. The potential role of the growth factor domain in the recognition of t-PA by the hepatic clearance mechanism is discussed.