Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor (original) (raw)

Abstract

Scatter Factor (SF) is a fibroblast-secreted protein which promotes motility and matrix invasion of epithelial cells. Hepatocyte Growth Factor (HGF) is a powerful mitogen for hepatocytes and other epithelial tissues. SF and HGF, purified according to their respective biological activities, were interchangeable and equally effective in assays for cell growth, motility and invasion. Both bound with identical affinities to the same sites in target cells. The receptor for SF and HGF was identified as the product of the MET oncogene by: (i) ligand binding and coprecipitation in immunocomplexes; (ii) chemical crosslinking to the Met beta subunit; (iii) transfer of binding activity in insect cells by a baculovirus carrying the MET cDNA; (iv) ligand-induced tyrosine phosphorylation of the Met beta subunit. SF and HGF cDNA clones from human fibroblasts, placenta and liver had virtually identical sequences. We conclude that the same molecule (SF/HGF) acts as a growth or motility factor through a single receptor in different target cells.

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Selected References

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  1. Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernier M., Laird D. M., Lane M. D. Insulin-activated tyrosine phosphorylation of a 15-kilodalton protein in intact 3T3-L1 adipocytes. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1844–1848. doi: 10.1073/pnas.84.7.1844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birchmeier C., O'Neill K., Riggs M., Wigler M. Characterization of ROS1 cDNA from a human glioblastoma cell line. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4799–4803. doi: 10.1073/pnas.87.12.4799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bottaro D. P., Rubin J. S., Faletto D. L., Chan A. M., Kmiecik T. E., Vande Woude G. F., Aaronson S. A. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991 Feb 15;251(4995):802–804. doi: 10.1126/science.1846706. [DOI] [PubMed] [Google Scholar]
  5. Comoglio P. M., Di Renzo M. F., Tarone G., Giancotti F. G., Naldini L., Marchisio P. C. Detection of phosphotyrosine-containing proteins in the detergent-insoluble fraction of RSV-transformed fibroblasts by azobenzene phosphonate antibodies. EMBO J. 1984 Mar;3(3):483–489. doi: 10.1002/j.1460-2075.1984.tb01834.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooper C. S., Park M., Blair D. G., Tainsky M. A., Huebner K., Croce C. M., Vande Woude G. F. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature. 1984 Sep 6;311(5981):29–33. doi: 10.1038/311029a0. [DOI] [PubMed] [Google Scholar]
  7. Cooper C. S., Tempest P. R., Beckman M. P., Heldin C. H., Brookes P. Amplification and overexpression of the met gene in spontaneously transformed NIH3T3 mouse fibroblasts. EMBO J. 1986 Oct;5(10):2623–2628. doi: 10.1002/j.1460-2075.1986.tb04543.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dean M., Park M., Le Beau M. M., Robins T. S., Diaz M. O., Rowley J. D., Blair D. G., Vande Woude G. F. The human met oncogene is related to the tyrosine kinase oncogenes. 1985 Nov 28-Dec 4Nature. 318(6044):385–388. doi: 10.1038/318385a0. [DOI] [PubMed] [Google Scholar]
  9. Di Renzo M. F., Ferracini R., Naldini L., Giordano S., Comoglio P. M. Immunological detection of proteins phosphorylated at tyrosine in cells stimulated by growth factors or transformed by retroviral-oncogene-coded tyrosine kinases. Eur J Biochem. 1986 Jul 15;158(2):383–391. doi: 10.1111/j.1432-1033.1986.tb09765.x. [DOI] [PubMed] [Google Scholar]
  10. Gandino L., Di Renzo M. F., Giordano S., Bussolino F., Comoglio P. M. Protein kinase-c activation inhibits tyrosine phosphorylation of the c-met protein. Oncogene. 1990 May;5(5):721–725. [PubMed] [Google Scholar]
  11. Garcia-Morales P., Minami Y., Luong E., Klausner R. D., Samelson L. E. Tyrosine phosphorylation in T cells is regulated by phosphatase activity: studies with phenylarsine oxide. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9255–9259. doi: 10.1073/pnas.87.23.9255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gherardi E., Gray J., Stoker M., Perryman M., Furlong R. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5844–5848. doi: 10.1073/pnas.86.15.5844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gherardi E., Stoker M. Hepatocytes and scatter factor. Nature. 1990 Jul 19;346(6281):228–228. doi: 10.1038/346228b0. [DOI] [PubMed] [Google Scholar]
  14. Giordano S., Di Renzo M. F., Ferracini R., Chiadò-Piat L., Comoglio P. M. p145, a protein with associated tyrosine kinase activity in a human gastric carcinoma cell line. Mol Cell Biol. 1988 Aug;8(8):3510–3517. doi: 10.1128/mcb.8.8.3510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Giordano S., Di Renzo M. F., Narsimhan R. P., Cooper C. S., Rosa C., Comoglio P. M. Biosynthesis of the protein encoded by the c-met proto-oncogene. Oncogene. 1989 Nov;4(11):1383–1388. [PubMed] [Google Scholar]
  16. Giordano S., Ponzetto C., Di Renzo M. F., Cooper C. S., Comoglio P. M. Tyrosine kinase receptor indistinguishable from the c-met protein. Nature. 1989 May 11;339(6220):155–156. doi: 10.1038/339155a0. [DOI] [PubMed] [Google Scholar]
  17. Gohda E., Tsubouchi H., Nakayama H., Hirono S., Sakiyama O., Takahashi K., Miyazaki H., Hashimoto S., Daikuhara Y. Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J Clin Invest. 1988 Feb;81(2):414–419. doi: 10.1172/JCI113334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gonzatti-Haces M., Seth A., Park M., Copeland T., Oroszlan S., Vande Woude G. F. Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1988 Jan;85(1):21–25. doi: 10.1073/pnas.85.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Greenfield C., Patel G., Clark S., Jones N., Waterfield M. D. Expression of the human EGF receptor with ligand-stimulatable kinase activity in insect cells using a baculovirus vector. EMBO J. 1988 Jan;7(1):139–146. doi: 10.1002/j.1460-2075.1988.tb02793.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Iyer A., Kmiecik T. E., Park M., Daar I., Blair D., Dunn K. J., Sutrave P., Ihle J. N., Bodescot M., Vande Woude G. F. Structure, tissue-specific expression, and transforming activity of the mouse met protooncogene. Cell Growth Differ. 1990 Feb;1(2):87–95. [PubMed] [Google Scholar]
  21. Kan M., Zhang G. H., Zarnegar R., Michalopoulos G., Myoken Y., McKeehan W. L., Stevens J. I. Hepatocyte growth factor/hepatopoietin A stimulates the growth of rat kidney proximal tubule epithelial cells (RPTE), rat nonparenchymal liver cells, human melanoma cells, mouse keratinocytes and stimulates anchorage-independent growth of SV-40 transformed RPTE. Biochem Biophys Res Commun. 1991 Jan 15;174(1):331–337. doi: 10.1016/0006-291x(91)90524-b. [DOI] [PubMed] [Google Scholar]
  22. Klein R., Jing S. Q., Nanduri V., O'Rourke E., Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell. 1991 Apr 5;65(1):189–197. doi: 10.1016/0092-8674(91)90419-y. [DOI] [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Michalopoulos G. K. Liver regeneration: molecular mechanisms of growth control. FASEB J. 1990 Feb 1;4(2):176–187. [PubMed] [Google Scholar]
  25. Miyazawa K., Tsubouchi H., Naka D., Takahashi K., Okigaki M., Arakaki N., Nakayama H., Hirono S., Sakiyama O., Takahashi K. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989 Sep 15;163(2):967–973. doi: 10.1016/0006-291x(89)92316-4. [DOI] [PubMed] [Google Scholar]
  26. Nakamura T., Nishizawa T., Hagiya M., Seki T., Shimonishi M., Sugimura A., Tashiro K., Shimizu S. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440–443. doi: 10.1038/342440a0. [DOI] [PubMed] [Google Scholar]
  27. Nakamura T., Teramoto H., Ichihara A. Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6489–6493. doi: 10.1073/pnas.83.17.6489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Naldini L., Vigna E., Ferracini R., Longati P., Gandino L., Prat M., Comoglio P. M. The tyrosine kinase encoded by the MET proto-oncogene is activated by autophosphorylation. Mol Cell Biol. 1991 Apr;11(4):1793–1803. doi: 10.1128/mcb.11.4.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Naldini L., Vigna E., Narsimhan R. P., Gaudino G., Zarnegar R., Michalopoulos G. K., Comoglio P. M. Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene. 1991 Apr;6(4):501–504. [PubMed] [Google Scholar]
  30. Park M., Dean M., Cooper C. S., Schmidt M., O'Brien S. J., Blair D. G., Vande Woude G. F. Mechanism of met oncogene activation. Cell. 1986 Jun 20;45(6):895–904. doi: 10.1016/0092-8674(86)90564-7. [DOI] [PubMed] [Google Scholar]
  31. Park M., Dean M., Kaul K., Braun M. J., Gonda M. A., Vande Woude G. Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379–6383. doi: 10.1073/pnas.84.18.6379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ponzetto C., Giordano S., Peverali F., Della Valle G., Abate M. L., Vaula G., Comoglio P. M. c-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. Oncogene. 1991 Apr;6(4):553–559. [PubMed] [Google Scholar]
  33. Rodrigues G. A., Naujokas M. A., Park M. Alternative splicing generates isoforms of the met receptor tyrosine kinase which undergo differential processing. Mol Cell Biol. 1991 Jun;11(6):2962–2970. doi: 10.1128/mcb.11.6.2962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rosen E. M., Meromsky L., Setter E., Vinter D. W., Goldberg I. D. Smooth muscle-derived factor stimulates mobility of human tumor cells. Invasion Metastasis. 1990;10(1):49–64. [PubMed] [Google Scholar]
  35. Rubin J. S., Chan A. M., Bottaro D. P., Burgess W. H., Taylor W. G., Cech A. C., Hirschfield D. W., Wong J., Miki T., Finch P. W. A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):415–419. doi: 10.1073/pnas.88.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ruoslahti E., Yamaguchi Y. Proteoglycans as modulators of growth factor activities. Cell. 1991 Mar 8;64(5):867–869. doi: 10.1016/0092-8674(91)90308-l. [DOI] [PubMed] [Google Scholar]
  37. Seki T., Ihara I., Sugimura A., Shimonishi M., Nishizawa T., Asami O., Hagiya M., Nakamura T., Shimizu S. Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte. Biochem Biophys Res Commun. 1990 Oct 15;172(1):321–327. doi: 10.1016/s0006-291x(05)80212-8. [DOI] [PubMed] [Google Scholar]
  38. Stern C. D., Ireland G. W., Herrick S. E., Gherardi E., Gray J., Perryman M., Stoker M. Epithelial scatter factor and development of the chick embryonic axis. Development. 1990 Dec;110(4):1271–1284. doi: 10.1242/dev.110.4.1271. [DOI] [PubMed] [Google Scholar]
  39. Stoker M., Gherardi E., Perryman M., Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature. 1987 May 21;327(6119):239–242. doi: 10.1038/327239a0. [DOI] [PubMed] [Google Scholar]
  40. Tashiro K., Hagiya M., Nishizawa T., Seki T., Shimonishi M., Shimizu S., Nakamura T. Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3200–3204. doi: 10.1073/pnas.87.8.3200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tempest P. R., Cooper C. S., Major G. N. The activated human met gene encodes a protein tyrosine kinase. FEBS Lett. 1986 Dec 15;209(2):357–361. doi: 10.1016/0014-5793(86)81142-5. [DOI] [PubMed] [Google Scholar]
  42. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  43. Weidner K. M., Behrens J., Vandekerckhove J., Birchmeier W. Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J Cell Biol. 1990 Nov;111(5 Pt 1):2097–2108. doi: 10.1083/jcb.111.5.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zarnegar R., DeFrances M. C., Oliver L., Michalopoulos G. Identification and partial characterization of receptor binding sites for HGF on rat hepatocytes. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1179–1185. doi: 10.1016/s0006-291x(05)80910-6. [DOI] [PubMed] [Google Scholar]
  45. Zarnegar R., Michalopoulos G. Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res. 1989 Jun 15;49(12):3314–3320. [PubMed] [Google Scholar]
  46. Zarnegar R., Muga S., Enghild J., Michalopoulos G. NH2-terminal amino acid sequence of rabbit hepatopoietin A, a heparin-binding polypeptide growth factor for hepatocytes. Biochem Biophys Res Commun. 1989 Sep 29;163(3):1370–1376. doi: 10.1016/0006-291x(89)91130-3. [DOI] [PubMed] [Google Scholar]
  47. Zarnegar R., Muga S., Rahija R., Michalopoulos G. Tissue distribution of hepatopoietin-A: a heparin-binding polypeptide growth factor for hepatocytes. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1252–1256. doi: 10.1073/pnas.87.3.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]