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Science 29 November 1991:
Vol. 254. no. 5036, pp. 1382 - 1385
DOI: 10.1126/science.1720571
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Articles

Science, Vol 254, Issue 5036, 1382-1385
Copyright © 1991 by American Association for the Advancement of Science

articles

Identification of a competitive HGF antagonist encoded by an alternative transcript

AM Chan, JS Rubin, DP Bottaro, DW Hirschfield, M Chedid, and SA Aaronson

Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.

We identified a naturally occurring hepatocyte growth factor (HGF) variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule. This smaller molecule, derived from an alternative HGF transcript, lacked mitogenic activity but specifically inhibited HGF-induced mitogenesis. Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the HGF receptor, which has been identified as the c-met protooncogene product. Thus, the same gene encodes both a growth factor and its direct antagonist.


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Fully Human Monoclonal Antibodies to Hepatocyte Growth Factor with Therapeutic Potential against Hepatocyte Growth Factor/c-Met-Dependent Human Tumors.
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Mast Cell and Neutrophil Peptidases Attack an Inactivation Segment in Hepatocyte Growth Factor to Generate NK4-like Antagonists.
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The Interactions of Hepatocyte Growth Factor/Scatter Factor and Its NK1 and NK2 Variants with Glycosaminoglycans Using a Modified Gel Mobility Shift Assay: ELUCIDATION OF THE MINIMAL SIZE OF BINDING AND ACTIVATORY OLIGOSACCHARIDES.
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Inhibition by Copper(II) Binding of Hepatocyte Growth Factor (HGF) Interaction with Its Receptor Met and Blockade of HGF/Met Function.
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A Lymphocyte-Generated Fragment of Vasoactive Intestinal Peptide with VPAC1 Agonist Activity and VPAC2 Antagonist Effects.
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Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3{beta}.
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Differential Mitogenic Effects of Single Chain Hepatocyte Growth Factor (HGF)/Scatter Factor and HGF/NK1 following Cleavage by Factor Xa.
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Hepatocyte Growth Factor/Scatter Factor Binds to Small Heparin-derived Oligosaccharides and Stimulates the Proliferation of Human HaCaT Keratinocytes.
M. Delehedde, M. Lyon, R. Vidyasagar, T. J. McDonnell, and D. G. Fernig (2002)
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HGF/NK4, a Four-Kringle Antagonist of Hepatocyte Growth Factor, Is an Angiogenesis Inhibitor that Suppresses Tumor Growth and Metastasis in Mice.
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J. Vivekananda, V. Awasthi, S. Awasthi, D. B. Smith, and R. J. King (2000)
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Antagonistic Effect of NK4, a Novel Hepatocyte Growth Factor Variant, on in Vitro Angiogenesis of Human Vascular Endothelial Cells.
W. G. Jiang, S. E. Hiscox, C. Parr, T. A. Martin, K. Matsumoto, T. Nakamura, and R. E. Mansel (1999)
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Interactions between scatter factors and their receptors: hints for therapeutic applications.
L. Trusolino, L. Pugliese, and P. M. Comoglio (1998)
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Cooperative Interaction between alpha - and beta -Chains of Hepatocyte Growth Factor on c-Met Receptor Confers Ligand-induced Receptor Tyrosine Phosphorylation and Multiple Biological Responses.
K. Matsumoto, H. Kataoka, K. Date, and T. Nakamura (1998)
J. Biol. Chem. 273, 22913-22920
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Developmental and Hormonal Regulation of Hepatocyte Growth Factor Expression and Action in the Bovine Ovarian Follicle.
J. A. Parrott and and M. K. Skinner (1998)
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NK1, a Natural Splice Variant of Hepatocyte Growth Factor/Scatter Factor, Is a Partial Agonist In Vivo.
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Functional Characterization of Domains Contained in Hepatocyte Growth Factor-like Protein.
S. E. Waltz, S. A. McDowell, R. S. Muraoka, E. L. Air, L. M. Flick, Y.-Q. Chen, M.-H. Wang, and S. J. F. Degen (1997)
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Heparin Binding and Oligomerization of Hepatocyte Growth Factor/Scatter Factor Isoforms. HEPARAN SULFATE GLYCOSAMINOGLYCAN REQUIREMENT FOR Met BINDING AND SIGNALING.
H. Sakata, S. J. Stahl, W. G. Taylor, J. M. Rosenberg, K. Sakaguchi, P. T. Wingfield, and J. S. Rubin (1997)
J. Biol. Chem. 272, 9457-9463
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Mechanisms of Hepatocyte Growth Factor Stimulation of Keratinocyte Metalloproteinase Production.
S. E. Dunsmore, J. S. Rubin, S. O. Kovacs, M. Chedid, W. C. Parks, and H. G. Welgus (1996)
J. Biol. Chem. 271, 24576-24582
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Branching Tubulogenesis but Not Scatter of Madin-Darby Canine Kidney Cells Requires a Functional Grb2 Binding Site in the Met Receptor Tyrosine Kinase.
T. M. Fournier, D. Kamikura, K. Teng, and M. Park (1996)
J. Biol. Chem. 271, 22211-22217
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Hepatocyte Growth Factor (HGF)/NK1 Is a Naturally Occurring HGF/Scatter Factor Variant with Partial Agonist/Antagonist Activity.
V. Cioce, K. G. Csaky, A. M.-L. Chan, D. P. Bottaro, W. G. Taylor, R. Jensen, S. A. Aaronson, and J. S. Rubin (1996)
J. Biol. Chem. 271, 13110-13115
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In Vivo Activation of met Tyrosine Kinase by Heterodimeric Hepatocyte Growth Factor Molecule Promotes Angiogenesis.
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A Novel Myocyte-specific Gene Midori Promotes the Differentiation of P19CL6 Cells into Cardiomyocytes.
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J. Biol. Chem. 276, 35978-35989
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Science. ISSN 0036-8075 (print), 1095-9203 (online)