Site-directed mutagenesis at 134/135 in human growth hormone alters its in vivo half-life in the rat.
It has been shown that human growth hormone (hGH) is attacked and digested at Arg(134)-Thr(135) by thrombin and plasmin, facilitating its further degradation in the plasma and tissues. To investigate the roles of the amino acids residues on the 134/135 site in the stability and half-life of the hormone in vivo, we have synthesized a mutant hGH, hGH(R134H, T135E), where Arg and Thr are replaced by His and Glu respectively. The mutant hGH showed an altered half-life time (7 min) as compared to that (11 min) for native form hGH, while the biological activity was not affected by the mutation.
Morimoto
M
M
Department of Biochemistrv, Mie University Faculty of Medicine, Tsu, Japan.
Tanaka
M
M
Nakashima
K
K
D000818:Animals; D006207:Half-Life; D019382:Human Growth Hormone / Q000235:genetics* / Q000493:pharmacokinetics; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D051381:Rats
D019382:Human Growth Hormone