Mammalian augmenter of liver regenerating and variants thereof.

摘要

Full-length cDNA clones have been isolated encoding purified augmenter of liver regeneration (ALR) polypeptides prepared from the cytosol of livers from weanling rats and from humans. The full-length clone from the rat is a 1226 bp cDNA containing an 81 bp 5'-untranslated region, a 594 bp coding region and a 551 bp 3'-untranslated region. The coding region encodes three proteins with estimated molecular weights of 15,081, 20,193 and 22,835. The molecular weight of the purified rat ALR protein was determined by SDS-PAGE to be 15,000 in the reduced form and 30,000 in the non-reduced form, indicating that ALR is a homodimer in its native state. The full-length clone from the human consists of a 727 bp cDNA containing a 4 bp 5'-untranslated region, a 615 bp coding region and a 108 bp 3'-untranslated region, including the termination codon TAG and the poly(A) region. The 615 bp coding region encodes four proteins, human ALR-V1, ALR-V2, ALR-V3 and ALR, having estimated molecular weights of 23,448, 20,834, 20,703 and 15,028, respectively. The recombinant ALR produced by expression of the cDNA in cultured cells was tested in vivo in the canine Eck's fistula model and found to have a potency equivalent to the purified native ALR. The most obvious immediate clinical use for the augmenter of liver regeneration is in the treatment of hepatic failure.