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Details

Autor(en) / Beteiligte
Titel
An engineered dimeric fragment of hepatocyte growth factor is a potent c-MET agonist
Ist Teil von
  • FEBS letters, 2014-12, Vol.588 (24), p.4831-4837
Ort / Verlag
England: Elsevier B.V
Erscheinungsjahr
2014
Link zum Volltext
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
  • •HGF is difficult to produce and unstable, highlighting a need for c-MET agonists.•A disulfide-linked dimer (eNK1 dimer) was created from an engineered HGF fragment.•The eNK1 monomer is a weak agonist and only activates c-MET at high concentrations.•The eNK1 dimer is a potent activator of c-MET, cell migration, and proliferation.•The eNK1 dimer elicits similar biological activity compared to HGF. 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.

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