Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1993 Apr 1;121(1):145–154. doi: 10.1083/jcb.121.1.145

The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells

PMCID: PMC2119778  PMID: 8384622

Abstract

Depending on the target cells and culture conditions, scatter factor/hepatocyte growth factor (SF/HGF) mediates several distinct activities, i.e., cell motility, proliferation, invasiveness, tubular morphogenesis, angiogenesis, or cytotoxicity. A small isoform of SF/HGF encoded by a natural splice variant, which consists of the NH2-terminal hairpin structure and the first two kringle domains but not the protease homology region, induces cell motility but not mitogenesis. Two types of SF/HGF receptors have recently been discovered in epithelial cells, the high affinity c-Met receptor tyrosine kinase, and low affinity/high capacity binding sites, which are probably located on heparan sulfate proteoglycans. In the present study, we have addressed the question whether the various biological activities of SF/HGF are transduced into cells by a single type of receptor. We have here examined MDCK epithelial cells transfected with a hybrid cDNA encoding the ligand binding domain of the nerve growth factor (NGF) receptor and the membrane-spanning and tyrosine kinase domains of the Met receptor. We demonstrate that all biological effects of SF/HGF upon epithelial cells such as the induction of cell motility, proliferation, invasiveness, and tubular morphogenesis can now be triggered by the addition of NGF. Thus, it is likely that all known biological signals of SF/HGF are transduced through the receptor tyrosine kinase encoded by the c-Met protooncogene.

Full Text

The Full Text of this article is available as a PDF (2.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Berhanu P., Rohilla A. M., Rutter W. J. Replacement of the human insulin receptor transmembrane and cytoplasmic domains by corresponding domains of the oncogene product v-ros leads to accelerated internalization, degradation, and down-regulation. J Biol Chem. 1990 Jun 5;265(16):9505–9511. [PubMed] [Google Scholar]
  3. 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]
  4. Bussolino F., Di Renzo M. F., Ziche M., Bocchietto E., Olivero M., Naldini L., Gaudino G., Tamagnone L., Coffer A., Comoglio P. M. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol. 1992 Nov;119(3):629–641. doi: 10.1083/jcb.119.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan A. M., King H. W., Deakin E. A., Tempest P. R., Hilkens J., Kroezen V., Edwards D. R., Wills A. J., Brookes P., Cooper C. S. Characterization of the mouse met proto-oncogene. Oncogene. 1988 Jun;2(6):593–599. [PubMed] [Google Scholar]
  6. Chan A. M., Rubin J. S., Bottaro D. P., Hirschfield D. W., Chedid M., Aaronson S. A. Identification of a competitive HGF antagonist encoded by an alternative transcript. Science. 1991 Nov 29;254(5036):1382–1385. doi: 10.1126/science.1720571. [DOI] [PubMed] [Google Scholar]
  7. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Cordon-Cardo C., Tapley P., Jing S. Q., Nanduri V., O'Rourke E., Lamballe F., Kovary K., Klein R., Jones K. R., Reichardt L. F. The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3. Cell. 1991 Jul 12;66(1):173–183. doi: 10.1016/0092-8674(91)90149-s. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ekblom P. Developmentally regulated conversion of mesenchyme to epithelium. FASEB J. 1989 Aug;3(10):2141–2150. doi: 10.1096/fasebj.3.10.2666230. [DOI] [PubMed] [Google Scholar]
  11. Ferracini R., Longati P., Naldini L., Vigna E., Comoglio P. M. Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinase. J Biol Chem. 1991 Oct 15;266(29):19558–19564. [PubMed] [Google Scholar]
  12. Furlong R. A., Takehara T., Taylor W. G., Nakamura T., Rubin J. S. Comparison of biological and immunochemical properties indicates that scatter factor and hepatocyte growth factor are indistinguishable. J Cell Sci. 1991 Sep;100(Pt 1):173–177. doi: 10.1242/jcs.100.1.173. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Gherardi E., Stoker M. Hepatocytes and scatter factor. Nature. 1990 Jul 19;346(6281):228–228. doi: 10.1038/346228b0. [DOI] [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. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  19. Gumbiner B. M. Epithelial morphogenesis. Cell. 1992 May 1;69(3):385–387. doi: 10.1016/0092-8674(92)90440-n. [DOI] [PubMed] [Google Scholar]
  20. Hartmann G., Naldini L., Weidner K. M., Sachs M., Vigna E., Comoglio P. M., Birchmeier W. A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11574–11578. doi: 10.1073/pnas.89.23.11574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Higashio K., Shima N., Goto M., Itagaki Y., Nagao M., Yasuda H., Morinaga T. Identity of a tumor cytotoxic factor from human fibroblasts and hepatocyte growth factor. Biochem Biophys Res Commun. 1990 Jul 16;170(1):397–404. doi: 10.1016/0006-291x(90)91287-3. [DOI] [PubMed] [Google Scholar]
  22. Holmes W. E., Sliwkowski M. X., Akita R. W., Henzel W. J., Lee J., Park J. W., Yansura D., Abadi N., Raab H., Lewis G. D. Identification of heregulin, a specific activator of p185erbB2. Science. 1992 May 22;256(5060):1205–1210. doi: 10.1126/science.256.5060.1205. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Johnson D., Lanahan A., Buck C. R., Sehgal A., Morgan C., Mercer E., Bothwell M., Chao M. Expression and structure of the human NGF receptor. Cell. 1986 Nov 21;47(4):545–554. doi: 10.1016/0092-8674(86)90619-7. [DOI] [PubMed] [Google Scholar]
  25. Kaplan D. R., Hempstead B. L., Martin-Zanca D., Chao M. V., Parada L. F. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science. 1991 Apr 26;252(5005):554–558. doi: 10.1126/science.1850549. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Klein R., Martin-Zanca D., Barbacid M., Parada L. F. Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system. Development. 1990 Aug;109(4):845–850. doi: 10.1242/dev.109.4.845. [DOI] [PubMed] [Google Scholar]
  28. Komada M., Miyazawa K., Ishii T., Kitamura N. Characterization of hepatocyte-growth-factor receptors on Meth A cells. Eur J Biochem. 1992 Mar 1;204(2):857–864. doi: 10.1111/j.1432-1033.1992.tb16705.x. [DOI] [PubMed] [Google Scholar]
  29. Konishi T., Takehara T., Tsuji T., Ohsato K., Matsumoto K., Nakamura T. Scatter factor from human embryonic lung fibroblasts is probably identical to hepatocyte growth factor. Biochem Biophys Res Commun. 1991 Oct 31;180(2):765–773. doi: 10.1016/s0006-291x(05)81131-3. [DOI] [PubMed] [Google Scholar]
  30. Lokker N. A., Mark M. R., Luis E. A., Bennett G. L., Robbins K. A., Baker J. B., Godowski P. J. Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding. EMBO J. 1992 Jul;11(7):2503–2510. doi: 10.1002/j.1460-2075.1992.tb05315.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Martin-Zanca D., Barbacid M., Parada L. F. Expression of the trk proto-oncogene is restricted to the sensory cranial and spinal ganglia of neural crest origin in mouse development. Genes Dev. 1990 May;4(5):683–694. doi: 10.1101/gad.4.5.683. [DOI] [PubMed] [Google Scholar]
  32. Martin-Zanca D., Oskam R., Mitra G., Copeland T., Barbacid M. Molecular and biochemical characterization of the human trk proto-oncogene. Mol Cell Biol. 1989 Jan;9(1):24–33. doi: 10.1128/mcb.9.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Miyazawa K., Kitamura A., Naka D., Kitamura N. An alternatively processed mRNA generated from human hepatocyte growth factor gene. Eur J Biochem. 1991 Apr 10;197(1):15–22. doi: 10.1111/j.1432-1033.1991.tb15876.x. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Mohammadi M., Dionne C. A., Li W., Li N., Spivak T., Honegger A. M., Jaye M., Schlessinger J. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature. 1992 Aug 20;358(6388):681–684. doi: 10.1038/358681a0. [DOI] [PubMed] [Google Scholar]
  36. Montesano R., Matsumoto K., Nakamura T., Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell. 1991 Nov 29;67(5):901–908. doi: 10.1016/0092-8674(91)90363-4. [DOI] [PubMed] [Google Scholar]
  37. Montesano R., Schaller G., Orci L. Induction of epithelial tubular morphogenesis in vitro by fibroblast-derived soluble factors. Cell. 1991 Aug 23;66(4):697–711. doi: 10.1016/0092-8674(91)90115-f. [DOI] [PubMed] [Google Scholar]
  38. Nagafuchi A., Takeichi M. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 1988 Dec 1;7(12):3679–3684. doi: 10.1002/j.1460-2075.1988.tb03249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nakamura T., Nawa K., Ichihara A., Kaise N., Nishino T. Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett. 1987 Nov 30;224(2):311–316. doi: 10.1016/0014-5793(87)80475-1. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. 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]
  43. Naldini L., Weidner K. M., Vigna E., Gaudino G., Bardelli A., Ponzetto C., Narsimhan R. P., Hartmann G., Zarnegar R., Michalopoulos G. K. Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J. 1991 Oct;10(10):2867–2878. doi: 10.1002/j.1460-2075.1991.tb07836.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. Peters K. G., Marie J., Wilson E., Ives H. E., Escobedo J., Del Rosario M., Mirda D., Williams L. T. Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis. Nature. 1992 Aug 20;358(6388):678–681. doi: 10.1038/358678a0. [DOI] [PubMed] [Google Scholar]
  46. Prat M., Crepaldi T., Gandino L., Giordano S., Longati P., Comoglio P. C-terminal truncated forms of Met, the hepatocyte growth factor receptor. Mol Cell Biol. 1991 Dec;11(12):5954–5962. doi: 10.1128/mcb.11.12.5954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Radeke M. J., Misko T. P., Hsu C., Herzenberg L. A., Shooter E. M. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature. 1987 Feb 12;325(6105):593–597. doi: 10.1038/325593a0. [DOI] [PubMed] [Google Scholar]
  48. Rapraeger A. C., Krufka A., Olwin B. B. Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation. Science. 1991 Jun 21;252(5013):1705–1708. doi: 10.1126/science.1646484. [DOI] [PubMed] [Google Scholar]
  49. Riedel H., Dull T. J., Honegger A. M., Schlessinger J., Ullrich A. Cytoplasmic domains determine signal specificity, cellular routing characteristics and influence ligand binding of epidermal growth factor and insulin receptors. EMBO J. 1989 Oct;8(10):2943–2954. doi: 10.1002/j.1460-2075.1989.tb08444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Roldan A. L., Cubellis M. V., Masucci M. T., Behrendt N., Lund L. R., Danø K., Appella E., Blasi F. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J. 1990 Feb;9(2):467–474. doi: 10.1002/j.1460-2075.1990.tb08132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Rosen E. M., Goldberg I. D., Kacinski B. M., Buckholz T., Vinter D. W. Smooth muscle releases an epithelial cell scatter factor which binds to heparin. In Vitro Cell Dev Biol. 1989 Feb;25(2):163–173. doi: 10.1007/BF02626174. [DOI] [PubMed] [Google Scholar]
  52. Rosen E. M., Meromsky L., Setter E., Vinter D. W., Goldberg I. D. Purified scatter factor stimulates epithelial and vascular endothelial cell migration. Proc Soc Exp Biol Med. 1990 Oct;195(1):34–43. doi: 10.3181/00379727-195-43115. [DOI] [PubMed] [Google Scholar]
  53. 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]
  54. 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]
  55. Shiota G., Rhoads D. B., Wang T. C., Nakamura T., Schmidt E. V. Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):373–377. doi: 10.1073/pnas.89.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sonnenberg E., Gödecke A., Walter B., Bladt F., Birchmeier C. Transient and locally restricted expression of the ros1 protooncogene during mouse development. EMBO J. 1991 Dec;10(12):3693–3702. doi: 10.1002/j.1460-2075.1991.tb04937.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sonnenberg E., Weidner K. M., Birchmeier C. Expression of the met-receptor and its ligand, HGF-SF during mouse embryogenesis. EXS. 1993;65:381–394. [PubMed] [Google Scholar]
  58. 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]
  59. 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]
  60. Tajima H., Matsumoto K., Nakamura T. Hepatocyte growth factor has potent anti-proliferative activity in various tumor cell lines. FEBS Lett. 1991 Oct 21;291(2):229–232. doi: 10.1016/0014-5793(91)81291-f. [DOI] [PubMed] [Google Scholar]
  61. Uehara Y., Kitamura N. Expression of a human hepatocyte growth factor/scatter factor cDNA in MDCK epithelial cells influences cell morphology, motility, and anchorage-independent growth. J Cell Biol. 1992 May;117(4):889–894. doi: 10.1083/jcb.117.4.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Vu T. K., Hung D. T., Wheaton V. I., Coughlin S. R. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991 Mar 22;64(6):1057–1068. doi: 10.1016/0092-8674(91)90261-v. [DOI] [PubMed] [Google Scholar]
  63. Weidner K. M., Arakaki N., Hartmann G., Vandekerckhove J., Weingart S., Rieder H., Fonatsch C., Tsubouchi H., Hishida T., Daikuhara Y. Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7001–7005. doi: 10.1073/pnas.88.16.7001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. 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]
  65. Wen D., Peles E., Cupples R., Suggs S. V., Bacus S. S., Luo Y., Trail G., Hu S., Silbiger S. M., Levy R. B. Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit. Cell. 1992 May 1;69(3):559–572. doi: 10.1016/0092-8674(92)90456-m. [DOI] [PubMed] [Google Scholar]
  66. Yayon A., Klagsbrun M., Esko J. D., Leder P., Ornitz D. M. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell. 1991 Feb 22;64(4):841–848. doi: 10.1016/0092-8674(91)90512-w. [DOI] [PubMed] [Google Scholar]
  67. 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]
  68. van Zonneveld A. J., Veerman H., Pannekoek H. Autonomous functions of structural domains on human tissue-type plasminogen activator. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4670–4674. doi: 10.1073/pnas.83.13.4670. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES