Processing of hepatocyte growth factor to the heterodimeric form is required for biological activity.
Hepatocyte growth factor is a plasminogen-like molecule with diverse biological effects. Although it is synthesized as a single chain polypeptide, it was originally purified as a disulfide-linked heterodimer which was generated by an internal proteolytic event. Subsequent work indicated that preparations consisting largely of the monomeric form also exhibited potent activity. By using a combination of protease inhibition and site-directed mutagenesis, we established that conversion of the single chain polypeptide to the heterodimer occurred during the bioassay and was required for mitogenic and motogenic activity.
Gak
E
E
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Taylor
W G
WG
Chan
A M
AM
Rubin
J S
JS
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001483:Base Sequence; D001681:Biological Assay; D002455:Cell Division / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011994:Recombinant Proteins / Q000096:biosynthesis
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D007611:Aprotinin