A tissue-type plasminogen activator mutant with prolonged clearance in vivo. Effect of removal of the growth factor domain

Autor: J H Robinson, C. Entwisle, G.M.P. Lawrence, C.G. Chapman, A.W.R. Tyrrell, M.J. Browne, B. Reavy, Ian B. Dodd, A.F. Esmail, J.E. Carey
Rok vydání: 1988
Předmět:
Zdroj: Journal of Biological Chemistry. 263:1599-1602
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(19)77918-6
Popis: 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.
Databáze: OpenAIRE