Lack of critical domains in the beta-chain of hepatocyte growth factor.
Hepatocyte growth factor (HGF) is a cytokine with pleiotropic effects on many different cell types. Its biological activities depend on the disulfide-linked alpha beta heterodimeric molecule. To study the functions of the beta-chain of HGF, insect cell-expressed HGFs prepared from nested deletions from C-terminus of beta-chain were studied for their biological activities and ligand-binding functions. The results demonstrated that the functions of HGF are dependent on the intactness of its beta-chain. The loss of HGF activities is correlated with the progressive deletion of beta-chain. There is not a single critical domain in the beta-chain that is essential for the functions of HGF. We propose that beta-chain may act to stabilize the ligand-receptor binding or contribute to the proper conformation of HGF to interact with its receptor.
Lee
H S
HS
Department of Internal Medicine, National Taiwan University, Taipei.
Huang
G T
GT
Sheu
J C
JC
Chiou
L L
LL
Horng
M C
MC
Lai
M Y
MY
Chen
D S
DS
Lee
S C
SC
D000818:Animals; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004285:Dogs; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008113:Liver Neoplasms; D046911:Macromolecular Substances; D051379:Mice; D016296:Mutagenesis; D019000:Phosphotyrosine; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D017384:Sequence Deletion; D018411:Spodoptera; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D046911:Macromolecular Substances; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases