TCF mutant

Abstract

The present invention relates to TCF mutant having a novel amino acid sequence which is obtained by mutagenesis of one or more amino acid between N-terminus and the first kringle of the amino acid sequence of native TCF and has lowered affinity to heparin and/or elevated biological activity. The present TCF mutant is prepared by gene manipulation of TCF. The TCF mutants of the present invention have proliferative activity and/or growth stimulative activity in hepatocyte and beneficial as a therapeutic agent for various hepatic diseases and an antitumor agent.

1 . A TCF mutant which is obtained by mutagenesis of more than one amino acid residue at the position from N-terminus to the first kringle of the amino acid sequence of native TCF and has lowered affinity to heparin and/or elevated biological activity.  
     
     
         2 . The TCF mutant according to  claim 1 , wherein Arg2-Lys-Arg-Arg5 of native TCF is mutagenized to Ala-Ala-Ala-Ala.  
     
     
         3 . The TCF mutant according to  claim 1 , wherein Lys27-Ile-Lys-Thr-Lys-Lys32 of native TCF is mutagenized to Ala-Ile-Ala-Thr-Ala-Ala.  
     
     
         4 . The TCF mutant according to  claim 2  or  3 , wherein proliferative activity thereof per unit amount of protein in hepatocyte is more than 10 folds than that of native TCF.  
     
     
         5 . The TCF mutant according to  claim 2  or  3 , wherein proliferative activity thereof per unit amount of protein in kidney epithelial cell is more than 2 folds than that of native TCF.  
     
     
         6 . The TCF mutant according to  claim 2  or  3 , wherein proliferative activity thereof per unit amount of protein in bone marrow cell is ½-{fraction (1/20)} of that of native TCF.  
     
     
         7 . The TCF mutant according to  claim 1 , wherein Lys54 of native TCF is mutagenized to Ala.  
     
     
         8 . The TCF mutant according to  claim 1 , wherein Argl32-Gly-Lys-Aspl35 of native TCF is mutagenized to Ala-Gly-Ala-Ala.  
     
     
         9 . The TCF mutant according to  claim 1 , wherein Argl42 of native TCF is mutagenized to Ala.  
     
     
         10 . The TCF mutant according to  claim 1 , wherein Arg42 of native TCF is mutagenized to Ala.