ArticleProceedings of the National Academy of Sciences of the United States of America2010
Structural basis for agonism and antagonism of hepatocyte growth factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 78 citations in OpenAlex.
- The Immediate Impact of Infarct Size on the Systemic Inflammatory Response: IL-6 as Central Mediator Identified through Biomarker and Proteomic Profiling.Journal of cardiovascular translational research · 2026Article
- In vitro immuno-prevention of nitration/dysfunction of myogenic stem cell activator HGF, towards developing a strategy for age-related muscle atrophy.Aging cell · 2024Article
- Article
- The Treatment of a New Entity in Advanced Non-small Cell Lung Cancer: MET Exon 14 Skipping Mutation.Current medicinal chemistry · 2024Review
- Cryo-electron Microscopic Analysis of Single-Pass Transmembrane Receptors.Chemical reviews · 2022Review
- A pilot study on nitration/dysfunction of NK1 segment of myogenic stem cell activator HGF.Biochemistry and biophysics reports · 2022Article
- Dimerization of kringle 1 domain from hepatocyte growth factor/scatter factor provides a potent MET receptor agonist.Life science alliance · 2022Article
- Modeling and dynamical analysis of the full-length structure of factor XII with zinc.Journal of molecular modeling · 2022Article
- Dynamic mRNA and miRNA expression of the head during early development in bighead carp (Hypophthalmichthys nobilis).BMC genomics · 2022Article
- Dimer Interface in Natural Variant NK1 Is Dispensable for HGF-Dependent Met Receptor Activation.International journal of molecular sciences · 2021Article
- Structural basis of the activation of c-MET receptor.Nature communications · 2021Article
- State of the structure address on MET receptor activation by HGF.Biochemical Society transactions · 2021Review
- MicroRNA-133b expression inversely correlates with MET and can serve as an optimum predictive biomarker for patients of colorectal cancer.Translational cancer research · 2021Article
- Development of bispecific anti-c-Met/PD-1 diabodies for the treatment of solid tumors and the effect of c-Met binding affinity on efficacy.Oncoimmunology · 2021Article
- Impaired ligand-dependent MET activation caused by an extracellular SEMA domain missense mutation in lung cancer.Cancer science · 2019Article
- A novel tetravalent bispecific antibody targeting programmed death 1 and tyrosine-protein kinase Met for treatment of gastric cancer.Investigational new drugs · 2019Article
- Verticillin A suppresses HGF-induced migration and invasion via repression of the c-Met/FAK/Src pathway in human gastric and cervical cancer cells.OncoTargets and therapy · 2019Article
- PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt.The Journal of experimental medicine · 2018Article
- MET Activation by a Macrocyclic Peptide Agonist that Couples to Biological Responses Differently from HGF in a Context-Dependent Manner.International journal of molecular sciences · 2018Article
- Hepatocyte Growth Factor Mediates Enhanced Wound Healing Responses and Resistance to Transforming Growth Factor-β₁-Driven Myofibroblast Differentiation in Oral Mucosal Fibroblasts.International journal of molecular sciences · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocyte growth factor (HGF) is an activating ligand of the Met receptor tyrosine kinase, whose activity is essential for normal tissue development and organ regeneration but abnormal activation of Met has been implicated in growth, invasion, and metastasis of many types of solid tumors. HGF has two natural splice variants, NK1 and NK2, which contain the N-terminal domain (N) and the first kringle (K1) or the first two kringle domains of HGF. NK1, which is a Met agonist, forms a head-to-tail dimer complex in crystal structures and mutations in the NK1 dimer interface convert NK1 to a Met antagonist. In contrast, NK2 is a Met antagonist, capable of inhibiting HGF's activity in cell proliferation without clear mechanism. Here we report the crystal structure of NK2, which forms a "closed" monomeric conformation through interdomain interactions between the N- domain and the second kringle domain (K2). Mutations that were designed to open up the NK2 closed conformation by disrupting the N/K2 interface convert NK2 from a Met antagonist to an agonist. Remarkably, this mutated NK2 agonist can be converted back to an antagonist by a mutation that disrupts the NK1/NK1 dimer interface. These results reveal the molecular determinants that regulate the agonist/antagonist properties of HGF NK2 and provide critical insights into the dimerization mechanism that regulates the Met receptor activation by HGF.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.