ArticleProceedings of the National Academy of Sciences of the United States of America2007
A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Dimer Interface in Natural Variant NK1 Is Dispensable for HGF-Dependent Met Receptor Activation.International journal of molecular sciences · 2021Article
- State of the structure address on MET receptor activation by HGF.Biochemical Society transactions · 2021Review
- Structural Basis of TPR-Mediated Oligomerization and Activation of Oncogenic Fusion Kinases.Structure (London, England : 1993) · 2017Article
- Utilizing combinatorial engineering to develop Tie2 targeting antagonistic angiopoetin-2 ligands as candidates for anti-angiogenesis therapy.Oncotarget · 2017Article
- Structural Basis for Interactions Between Contactin Family Members and Protein-tyrosine Phosphatase Receptor Type G in Neural Tissues.The Journal of biological chemistry · 2016Article
- Analogs of the hepatocyte growth factor and macrophage-stimulating protein hinge regions act as Met and Ron dual inhibitors in pancreatic cancer cells.Anti-cancer drugs · 2016Article
- Flexibility and small pockets at protein-protein interfaces: New insights into druggability.Progress in biophysics and molecular biology · 2015Review
- Physiological Signaling and Structure of the HGF Receptor MET.Biomedicines · 2014Review
- An engineered dimeric fragment of hepatocyte growth factor is a potent c-MET agonist.FEBS letters · 2014Article
- MET: a critical player in tumorigenesis and therapeutic target.Cold Spring Harbor perspectives in biology · 2013Review
- Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells.BMC biophysics · 2013Article
- Targeting the HGF-cMET Axis in Hepatocellular Carcinoma.International journal of hepatology · 2013Article
- Plexin structures are coming: opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions.Cellular and molecular life sciences : CMLS · 2012Review
- Engineered variants of InlB with an additional leucine-rich repeat discriminate between physiologically relevant and packing contacts in crystal structures of the InlB:MET complex.Protein science : a publication of the Protein Society · 2012Article
- Targeting MET in cancer: rationale and progress.Nature reviews. Cancer · 2012Review
- Engineering hepatocyte growth factor fragments with high stability and activity as Met receptor agonists and antagonists.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- A role for septins in the interaction between the Listeria monocytogenes INVASION PROTEIN InlB and the Met receptor.Biophysical journal · 2011Article
- Allosteric peptide activators of pro-hepatocyte growth factor stimulate Met signaling.The Journal of biological chemistry · 2010Article
- Structural basis for agonism and antagonism of hepatocyte growth factor.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- The angiotensin IV analog Nle-Tyr-Leu-psi-(CH2-NH2)3-4-His-Pro-Phe (norleual) can act as a hepatocyte growth factor/c-Met inhibitor.The Journal of pharmacology and experimental therapeutics · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocyte growth factor (HGF) activates the Met receptor tyrosine kinase by binding and promoting receptor dimerization. Here we describe a mechanistic basis for designing Met antagonists based on NK1, a natural variant of HGF containing the N-terminal and the first kringle domain. Through detailed biochemical and structural analyses, we demonstrate that both mouse and human NK1 induce Met dimerization via a conserved NK1 dimer interface. Mutations designed to alter the NK1 dimer interface abolish its ability to promote Met dimerization but retain full Met-binding activity. Importantly, these NK1 mutants act as Met antagonists by inhibiting HGF-mediated cell scattering, proliferation, branching, and invasion. The ability to separate the Met-binding activity of NK1 from its Met dimerization activity thus provides a rational basis for designing Met antagonists. This strategy of antagonist design may be applicable for other growth factor receptors by selectively abolishing the receptor activation ability but not the receptor binding of the growth factors.
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Registered trials
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.