ArticleMolecular and cellular biology1998
NK1, a natural splice variant of hepatocyte growth factor/scatter factor, is a partial agonist in vivo.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 58 citations in OpenAlex.
- A pilot study on nitration/dysfunction of NK1 segment of myogenic stem cell activator HGF.Biochemistry and biophysics reports · 2022Article
- Review
- Exploring the chemical space of the lysine-binding pocket of the first kringle domain of hepatocyte growth factor/scatter factor (HGF/SF) yields a new class of inhibitors of HGF/SF-MET binding.Chemical science · 2015Article
- An engineered dimeric fragment of hepatocyte growth factor is a potent c-MET agonist.FEBS letters · 2014Article
- Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling.Biomedicines · 2014Review
- Prenatal expression of MET receptor tyrosine kinase in the fetal mouse dorsal raphe nuclei and the visceral motor/sensory brainstem.Developmental neuroscience · 2013Article
- dsAAV8-mediated gene transfer and β-cell expression of IL-4 and β-cell growth factors are capable of reversing early-onset diabetes in NOD mice.Gene therapy · 2012Article
- Targeting MET in cancer: rationale and progress.Nature reviews. Cancer · 2012Review
- Article
- Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39.American journal of human genetics · 2009Article
- A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Differential mitogenic effects of single chain hepatocyte growth factor (HGF)/scatter factor and HGF/NK1 following cleavage by factor Xa.The Journal of biological chemistry · 2002Article
- Article
- SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma.World journal of gastroenterology · 2001Article
- Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor.The EMBO journal · 2001Article
- Disassociation of met-mediated biological responses in vivo: the natural hepatocyte growth factor/scatter factor splice variant NK2 antagonizes growth but facilitates metastasis.Molecular and cellular biology · 2000Article
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen, motogen, and morphogen for epithelial cells expressing its tyrosine kinase receptor, the c-met proto-oncogene product, and is required for normal development in the mouse. Inappropriate stimulation of Met signal transduction induces aberrant morphogenesis and oncogenesis in mice and has been implicated in human cancer. NK1 is a naturally occurring HGF/SF splice variant composed of only the amino terminus and first kringle domain. While the biological activities of NK1 have been controversial, in vitro data suggest that it may have therapeutic value as an HGF/SF antagonist. Here, we directly test this hypothesis in vivo by expressing mouse NK1 in transgenic mice and comparing the consequent effects with those observed for mice carrying an HGF/SF transgene. Despite robust expression, NK1 did not behave as an HGF/SF antagonist in vivo. Instead, NK1-transgenic mice displayed most of the phenotypic characteristics associated with HGF/SF-transgenic mice, including enlarged livers, ectopic skeletal-muscle formation, progressive renal disease, aberrant pigment cell localization, precocious mammary lobuloalveolar development, and the appearance of mammary, hepatocellular, and melanocytic tumors. And like HGF/SF-transgenic livers, NK1 livers had higher levels of tyrosine-phosphorylated complexes associated with Met, suggesting that the mechanistic basis for the effects of NK1 overexpression in vivo was autocrine activation of Met. We conclude that NK1 acts in vivo as a partial agonist. As such, the efficacy of NK1 as a therapeutic HGF/SF antagonist must be seriously questioned.
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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.