title: An engineered dimeric fragment of hepatocyte growth factor is a potent c-MET agonist.
abstract: Hepatocyte growth factor (HGF), through activation of the c-MET receptor, mediates biological processes critical for tissue regeneration; however, its clinical application is limited by protein instability and poor recombinant expression. We previously engineered an HGF fragment (eNK1) that possesses increased stability and expression yield and developed a c-MET agonist by coupling eNK1 through an introduced cysteine residue. Here, we further characterize this eNK1 dimer and show it elicits significantly greater c-MET activation, cell migration, and proliferation than the eNK1 monomer. The efficacy of the eNK1 dimer was similar to HGF, suggesting its promise as a c-MET agonist.
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, CA, United States.
authors.forename: Cassie J
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA, United States.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Jones
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA, United States.
authors.forename: Ping-Chuan
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA, United States.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Venkataramana
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, CA, United States; Department of Bioengineering, Stanford University, Stanford, CA, United States. Electronic address: jennifer.cochran@stanford.edu.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Cochran
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015202:Protein Engineering; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D019859:Proto-Oncogene Proteins c-met / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013696:Temperature
chemical_list: D010446:Peptide Fragments; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Hepatocyte growth factor; Ligand/receptor interaction; Protein engineering; Receptor agonist; Tissue regeneration; c-MET receptor