Scatter Factor and Hepatocyte Growth Factor Are Indistinguishable Ligands for the MET Receptor

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1991 Oct 1

PMID 1655405

Citations 196

Authors

L Naldini

K M Weidner

E Vigna

G Gaudino

A Bardelli

C Ponzetto

R P Narsimhan

G Hartmann

R Zarnegar

G K Michalopoulos

Affiliations

Soon will be listed here.

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.

Citing Articles

The MET Oncogene: An Update on Targeting Strategies.

Gallo S, Folco C, Crepaldi T Pharmaceuticals (Basel). 2024; 17(11).

PMID: 39598385 PMC: 11597589. DOI: 10.3390/ph17111473.

Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions.

Wang K, Hsu R Antibodies (Basel). 2024; 13(4).

PMID: 39449330 PMC: 11503282. DOI: 10.3390/antib13040088.

The rapidly changing field of predictive biomarkers of non-small cell lung cancer.

Toth L, Mokanszki A, Mehes G Pathol Oncol Res. 2024; 30:1611733.

PMID: 38953007 PMC: 11215025. DOI: 10.3389/pore.2024.1611733.

MET Oncogene Targeting for Cancer Immunotherapy.

Lombardi A, Sangiolo D, Vigna E Int J Mol Sci. 2024; 25(11).

PMID: 38892318 PMC: 11173045. DOI: 10.3390/ijms25116109.

The MET Oncogene: Thirty Years of Insights into Molecular Mechanisms Driving Malignancy.

Crepaldi T, Gallo S, Comoglio P Pharmaceuticals (Basel). 2024; 17(4).

PMID: 38675409 PMC: 11054789. DOI: 10.3390/ph17040448.

References

Ponzetto C, Giordano S, Peverali F, Della Valle G, Abate M, Vaula G . c-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. Oncogene. 1991; 6(4):553-9. View

Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A . Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989; 342(6248):440-3. DOI: 10.1038/342440a0. View

Klein R, Jing S, Nanduri V, ORourke E, Barbacid M . The trk proto-oncogene encodes a receptor for nerve growth factor. Cell. 1991; 65(1):189-97. DOI: 10.1016/0092-8674(91)90419-y. View

Rodrigues G, Naujokas M, Park M . Alternative splicing generates isoforms of the met receptor tyrosine kinase which undergo differential processing. Mol Cell Biol. 1991; 11(6):2962-70. PMC: 360125. DOI: 10.1128/mcb.11.6.2962-2970.1991. View

Iyer A, Kmiecik T, Park M, Daar I, Blair D, Dunn K . Structure, tissue-specific expression, and transforming activity of the mouse met protooncogene. Cell Growth Differ. 1990; 1(2):87-95. View

Naldini L, Vigna E, Ferracini R, Longati P, Gandino L, Prat M . The tyrosine kinase encoded by the MET proto-oncogene is activated by autophosphorylation. Mol Cell Biol. 1991; 11(4):1793-803. PMC: 359847. DOI: 10.1128/mcb.11.4.1793-1803.1991. View

Bottaro D, Rubin J, Faletto D, Chan A, Kmiecik T, Woude G . Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991; 251(4995):802-4. DOI: 10.1126/science.1846706. View

Zarnegar R, Defrances M, Oliver L, Michalopoulos G . Identification and partial characterization of receptor binding sites for HGF on rat hepatocytes. Biochem Biophys Res Commun. 1990; 173(3):1179-85. DOI: 10.1016/s0006-291x(05)80910-6. View

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; 86(15):5844-8. PMC: 297727. DOI: 10.1073/pnas.86.15.5844. View

10.

Behrens J, Mareel M, van Roy F, Birchmeier W . Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989; 108(6):2435-47. PMC: 2115620. DOI: 10.1083/jcb.108.6.2435. View

11.

Seth A, Park M, Copeland T, Oroszlan S, Woude G . Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1988; 85(1):21-5. PMC: 279473. DOI: 10.1073/pnas.85.1.21. View

12.

Giordano S, Di Renzo M, Ferracini R, Comoglio P . p145, a protein with associated tyrosine kinase activity in a human gastric carcinoma cell line. Mol Cell Biol. 1988; 8(8):3510-7. PMC: 363588. DOI: 10.1128/mcb.8.8.3510-3517.1988. View

13.

Tempest P, Cooper C, Major G . The activated human met gene encodes a protein tyrosine kinase. FEBS Lett. 1986; 209(2):357-61. DOI: 10.1016/0014-5793(86)81142-5. View

14.

Naldini L, Vigna E, Narsimhan R, Gaudino G, Zarnegar R, Michalopoulos G . Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene. 1991; 6(4):501-4. View

15.

Garcia-Morales P, Minami Y, Luong E, Klausner R, Samelson L . Tyrosine phosphorylation in T cells is regulated by phosphatase activity: studies with phenylarsine oxide. Proc Natl Acad Sci U S A. 1990; 87(23):9255-9. PMC: 55143. DOI: 10.1073/pnas.87.23.9255. View

16.

Kan M, Zhang G, Zarnegar R, Michalopoulos G, Myoken Y, McKeehan W . 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.... Biochem Biophys Res Commun. 1991; 174(1):331-7. DOI: 10.1016/0006-291x(91)90524-b. View

17.

Ullrich A, Schlessinger J . Signal transduction by receptors with tyrosine kinase activity. Cell. 1990; 61(2):203-12. DOI: 10.1016/0092-8674(90)90801-k. View

18.

Gherardi E, Stoker M . Hepatocytes and scatter factor. Nature. 1990; 346(6281):228. DOI: 10.1038/346228b0. View

19.

Tashiro K, Hagiya M, Nishizawa T, Seki T, Shimonishi M, Shimizu S . Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues. Proc Natl Acad Sci U S A. 1990; 87(8):3200-4. PMC: 53863. DOI: 10.1073/pnas.87.8.3200. View

20.

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; 87(3):1252-6. PMC: 53449. DOI: 10.1073/pnas.87.3.1252. View