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. 1994 Dec 2;127(6):1743–1754. doi: 10.1083/jcb.127.6.1743

Hepatocyte growth factor induces proliferation and differentiation of multipotent and erythroid hemopoietic progenitors

PMCID: PMC2120271  PMID: 7528222

Abstract

Hepatocyte growth factor (HGF) is a mesenchymal derived growth factor known to induce proliferation and "scattering" of epithelial and endothelial cells. Its receptor is the tyrosine kinase encoded by the c- MET protooncogene. Here we show that highly purified recombinant HGF stimulates hemopoietic progenitors to form colonies in vitro. In the presence of erythropoietin, picomolar concentrations of HGF induced the formation of erythroid burst-forming unit colonies from CD34-positive cells purified from human bone marrow, peripheral blood, or umbilical cord blood. The growth stimulatory activity was restricted to the erythroid lineage. HGF also stimulated the formation of multipotent CFU- GEMM colonies. This effect is synergized by stem cell factor, the ligand of the tyrosine kinase receptor encoded by the c-KIT protooncogene, which is active on early hemopoietic progenitors. By flow cytometry analysis, the receptor for HGF was found to be expressed on the cell surface in a fraction of CD34+ progenitors. Moreover, in situ hybridization experiments showed that HGF receptor mRNA is highly expressed in embryonic erythroid cells (megaloblasts). HGF mRNA was also found to be produced in the embryonal liver. These data show that HGF plays a direct role in the control of proliferation and differentiation of erythroid progenitors, and they suggest that it may be one of the long-sought mediators of paracrine interactions between stromal and hemopoietic cells within the hemopoietic microenvironment.

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Selected References

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  1. Aprelikova O., Pajusola K., Partanen J., Armstrong E., Alitalo R., Bailey S. K., McMahon J., Wasmuth J., Huebner K., Alitalo K. FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter. Cancer Res. 1992 Feb 1;52(3):746–748. [PubMed] [Google Scholar]
  2. Bagnara G. P., Zauli G., Vitale L., Rosito P., Vecchi V., Paolucci G., Avanzi G. C., Ramenghi U., Timeus F., Gabutti V. In vitro growth and regulation of bone marrow enriched CD34+ hematopoietic progenitors in Diamond-Blackfan anemia. Blood. 1991 Nov 1;78(9):2203–2210. [PubMed] [Google Scholar]
  3. Bardelli A., Maina F., Gout I., Fry M. J., Waterfield M. D., Comoglio P. M., Ponzetto C. Autophosphorylation promotes complex formation of recombinant hepatocyte growth factor receptor with cytoplasmic effectors containing SH2 domains. Oncogene. 1992 Oct;7(10):1973–1978. [PubMed] [Google Scholar]
  4. Besmer P. The kit ligand encoded at the murine Steel locus: a pleiotropic growth and differentiation factor. Curr Opin Cell Biol. 1991 Dec;3(6):939–946. doi: 10.1016/0955-0674(91)90111-b. [DOI] [PubMed] [Google Scholar]
  5. Boccaccio C., Gaudino G., Gambarotta G., Galimi F., Comoglio P. M. Hepatocyte growth factor (HGF) receptor expression is inducible and is part of the delayed-early response to HGF. J Biol Chem. 1994 Apr 29;269(17):12846–12851. [PubMed] [Google Scholar]
  6. Bot F. J., Dorssers L., Wagemaker G., Löwenberg B. Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow precursors: importance of accessory cells. Blood. 1988 Jun;71(6):1609–1614. [PubMed] [Google Scholar]
  7. 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]
  8. Briddell R. A., Broudy V. C., Bruno E., Brandt J. E., Srour E. F., Hoffman R. Further phenotypic characterization and isolation of human hematopoietic progenitor cells using a monoclonal antibody to the c-kit receptor. Blood. 1992 Jun 15;79(12):3159–3167. [PubMed] [Google Scholar]
  9. Brizzi M. F., Avanzi G. C., Pegoraro L. Hematopoietic growth factor receptors. Int J Cell Cloning. 1991 Jul;9(4):274–300. doi: 10.1002/stem.5530090404. [DOI] [PubMed] [Google Scholar]
  10. Broxmeyer H. E., Hangoc G., Cooper S., Ribeiro R. C., Graves V., Yoder M., Wagner J., Vadhan-Raj S., Benninger L., Rubinstein P. Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4109–4113. doi: 10.1073/pnas.89.9.4109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Broxmeyer H. E., Maze R., Miyazawa K., Carow C., Hendrie P. C., Cooper S., Hangoc G., Vadhan-Raj S., Lu L. The kit receptor and its ligand, steel factor, as regulators of hemopoiesis. Cancer Cells. 1991 Dec;3(12):480–487. [PubMed] [Google Scholar]
  12. 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]
  13. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  14. Chabot B., Stephenson D. A., Chapman V. M., Besmer P., Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988 Sep 1;335(6185):88–89. doi: 10.1038/335088a0. [DOI] [PubMed] [Google Scholar]
  15. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  16. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  17. Correa P. N., Axelrad A. A. Production of erythropoietic bursts by progenitor cells from adult human peripheral blood in an improved serum-free medium: role of insulinlike growth factor 1. Blood. 1991 Dec 1;78(11):2823–2833. [PubMed] [Google Scholar]
  18. Di Renzo M. F., Narsimhan R. P., Olivero M., Bretti S., Giordano S., Medico E., Gaglia P., Zara P., Comoglio P. M. Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene. 1991 Nov;6(11):1997–2003. [PubMed] [Google Scholar]
  19. 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]
  20. Flanagan J. G., Chan D. C., Leder P. Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell. 1991 Mar 8;64(5):1025–1035. doi: 10.1016/0092-8674(91)90326-t. [DOI] [PubMed] [Google Scholar]
  21. Gambarotta G., Pistoi S., Giordano S., Comoglio P. M., Santoro C. Structure and inducible regulation of the human MET promoter. J Biol Chem. 1994 Apr 29;269(17):12852–12857. [PubMed] [Google Scholar]
  22. 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]
  23. Gandino L., Longati P., Medico E., Prat M., Comoglio P. M. Phosphorylation of serine 985 negatively regulates the hepatocyte growth factor receptor kinase. J Biol Chem. 1994 Jan 21;269(3):1815–1820. [PubMed] [Google Scholar]
  24. Gandino L., Munaron L., Naldini L., Ferracini R., Magni M., Comoglio P. M. Intracellular calcium regulates the tyrosine kinase receptor encoded by the MET oncogene. J Biol Chem. 1991 Aug 25;266(24):16098–16104. [PubMed] [Google Scholar]
  25. Gasson J. C. Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood. 1991 Mar 15;77(6):1131–1145. [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. 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]
  29. Giordano S., Zhen Z., Medico E., Gaudino G., Galimi F., Comoglio P. M. Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):649–653. doi: 10.1073/pnas.90.2.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Grant D. S., Kleinman H. K., Goldberg I. D., Bhargava M. M., Nickoloff B. J., Kinsella J. L., Polverini P., Rosen E. M. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937–1941. doi: 10.1073/pnas.90.5.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Graziani A., Gramaglia D., Cantley L. C., Comoglio P. M. The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase. J Biol Chem. 1991 Nov 25;266(33):22087–22090. [PubMed] [Google Scholar]
  33. Graziani A., Gramaglia D., dalla Zonca P., Comoglio P. M. Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide exchanger. J Biol Chem. 1993 May 5;268(13):9165–9168. [PubMed] [Google Scholar]
  34. Halaban R., Rubin J. S., Funasaka Y., Cobb M., Boulton T., Faletto D., Rosen E., Chan A., Yoko K., White W. Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. Oncogene. 1992 Nov;7(11):2195–2206. [PubMed] [Google Scholar]
  35. Huang E. J., Nocka K. H., Buck J., Besmer P. Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. Mol Biol Cell. 1992 Mar;3(3):349–362. doi: 10.1091/mbc.3.3.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Iscove N. N., Sieber F., Winterhalter K. H. Erythroid colony formation in cultures of mouse and human bone marrow: analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose-concanavalin A. J Cell Physiol. 1974 Apr;83(2):309–320. doi: 10.1002/jcp.1040830218. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Kmiecik T. E., Keller J. R., Rosen E., Vande Woude G. F. Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells. Blood. 1992 Nov 15;80(10):2454–2457. [PubMed] [Google Scholar]
  39. Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
  40. Koury M. J., Bondurant M. C. Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science. 1990 Apr 20;248(4953):378–381. doi: 10.1126/science.2326648. [DOI] [PubMed] [Google Scholar]
  41. Lev S., Givol D., Yarden Y. A specific combination of substrates is involved in signal transduction by the kit-encoded receptor. EMBO J. 1991 Mar;10(3):647–654. doi: 10.1002/j.1460-2075.1991.tb07993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Longati P., Bardelli A., Ponzetto C., Naldini L., Comoglio P. M. Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by the MET proto-oncogene (HGF receptor). Oncogene. 1994 Jan;9(1):49–57. [PubMed] [Google Scholar]
  43. Lu L., Xiao M., Shen R. N., Grigsby S., Broxmeyer H. E. Enrichment, characterization, and responsiveness of single primitive CD34 human umbilical cord blood hematopoietic progenitors with high proliferative and replating potential. Blood. 1993 Jan 1;81(1):41–48. [PubMed] [Google Scholar]
  44. Martin D. I., Tsai S. F., Orkin S. H. Increased gamma-globin expression in a nondeletion HPFH mediated by an erythroid-specific DNA-binding factor. Nature. 1989 Mar 30;338(6214):435–438. doi: 10.1038/338435a0. [DOI] [PubMed] [Google Scholar]
  45. Matsumoto K., Hashimoto K., Yoshikawa K., Nakamura T. Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor. Exp Cell Res. 1991 Sep;196(1):114–120. doi: 10.1016/0014-4827(91)90462-4. [DOI] [PubMed] [Google Scholar]
  46. Matthews W., Jordan C. T., Gavin M., Jenkins N. A., Copeland N. G., Lemischka I. R. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9026–9030. doi: 10.1073/pnas.88.20.9026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. McNiece I. K., Langley K. E., Zsebo K. M. Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. Exp Hematol. 1991 Mar;19(3):226–231. [PubMed] [Google Scholar]
  48. Metcalf D. The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature. 1989 May 4;339(6219):27–30. doi: 10.1038/339027a0. [DOI] [PubMed] [Google Scholar]
  49. Miyajima A., Mui A. L., Ogorochi T., Sakamaki K. Receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5. Blood. 1993 Oct 1;82(7):1960–1974. [PubMed] [Google Scholar]
  50. Miyazawa K., Shimomura T., Kitamura A., Kondo J., Morimoto Y., Kitamura N. Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. J Biol Chem. 1993 May 15;268(14):10024–10028. [PubMed] [Google Scholar]
  51. 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]
  52. Mizuno K., Takehara T., Nakamura T. Proteolytic activation of a single-chain precursor of hepatocyte growth factor by extracellular serine-protease. Biochem Biophys Res Commun. 1992 Dec 30;189(3):1631–1638. doi: 10.1016/0006-291x(92)90264-l. [DOI] [PubMed] [Google Scholar]
  53. Mizuno K., Tanoue Y., Okano I., Harano T., Takada K., Nakamura T. Purification and characterization of hepatocyte growth factor (HGF)-converting enzyme: activation of pro-HGF. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1161–1169. doi: 10.1006/bbrc.1994.1164. [DOI] [PubMed] [Google Scholar]
  54. 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]
  55. Morimoto A., Okamura K., Hamanaka R., Sato Y., Shima N., Higashio K., Kuwano M. Hepatocyte growth factor modulates migration and proliferation of human microvascular endothelial cells in culture. Biochem Biophys Res Commun. 1991 Sep 16;179(2):1042–1049. doi: 10.1016/0006-291x(91)91924-2. [DOI] [PubMed] [Google Scholar]
  56. Naka D., Ishii T., Yoshiyama Y., Miyazawa K., Hara H., Hishida T., Kidamura N. Activation of hepatocyte growth factor by proteolytic conversion of a single chain form to a heterodimer. J Biol Chem. 1992 Oct 5;267(28):20114–20119. [PubMed] [Google Scholar]
  57. 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]
  58. Naldini L., Tamagnone L., Vigna E., Sachs M., Hartmann G., Birchmeier W., Daikuhara Y., Tsubouchi H., Blasi F., Comoglio P. M. Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. EMBO J. 1992 Dec;11(13):4825–4833. doi: 10.1002/j.1460-2075.1992.tb05588.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. 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]
  60. 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]
  61. Noji S., Tashiro K., Koyama E., Nohno T., Ohyama K., Taniguchi S., Nakamura T. Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization. Biochem Biophys Res Commun. 1990 Nov 30;173(1):42–47. doi: 10.1016/s0006-291x(05)81018-6. [DOI] [PubMed] [Google Scholar]
  62. 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]
  63. Pawson T., Schlessingert J. SH2 and SH3 domains. Curr Biol. 1993 Jul 1;3(7):434–442. doi: 10.1016/0960-9822(93)90350-w. [DOI] [PubMed] [Google Scholar]
  64. Pepper M. S., Matsumoto K., Nakamura T., Orci L., Montesano R. Hepatocyte growth factor increases urokinase-type plasminogen activator (u-PA) and u-PA receptor expression in Madin-Darby canine kidney epithelial cells. J Biol Chem. 1992 Oct 5;267(28):20493–20496. [PubMed] [Google Scholar]
  65. Ponzetto C., Bardelli A., Maina F., Longati P., Panayotou G., Dhand R., Waterfield M. D., Comoglio P. M. A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor. Mol Cell Biol. 1993 Aug;13(8):4600–4608. doi: 10.1128/mcb.13.8.4600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Ponzetto C., Bardelli A., Zhen Z., Maina F., dalla Zonca P., Giordano S., Graziani A., Panayotou G., Comoglio P. M. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell. 1994 Apr 22;77(2):261–271. doi: 10.1016/0092-8674(94)90318-2. [DOI] [PubMed] [Google Scholar]
  67. 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]
  68. Prat M., Narsimhan R. P., Crepaldi T., Nicotra M. R., Natali P. G., Comoglio P. M. The receptor encoded by the human c-MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors. Int J Cancer. 1991 Sep 30;49(3):323–328. doi: 10.1002/ijc.2910490302. [DOI] [PubMed] [Google Scholar]
  69. Rosnet O., Matteï M. G., Marchetto S., Birnbaum D. Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene. Genomics. 1991 Feb;9(2):380–385. doi: 10.1016/0888-7543(91)90270-o. [DOI] [PubMed] [Google Scholar]
  70. Rottapel R., Reedijk M., Williams D. E., Lyman S. D., Anderson D. M., Pawson T., Bernstein A. The Steel/W transduction pathway: kit autophosphorylation and its association with a unique subset of cytoplasmic signaling proteins is induced by the Steel factor. Mol Cell Biol. 1991 Jun;11(6):3043–3051. doi: 10.1128/mcb.11.6.3043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. 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]
  72. Sherr C. J. Colony-stimulating factor-1 receptor. Blood. 1990 Jan 1;75(1):1–12. [PubMed] [Google Scholar]
  73. Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., Sato M. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. 1990 Apr;5(4):519–524. [PubMed] [Google Scholar]
  74. Shimomura T., Kondo J., Ochiai M., Naka D., Miyazawa K., Morimoto Y., Kitamura N. Activation of the zymogen of hepatocyte growth factor activator by thrombin. J Biol Chem. 1993 Oct 25;268(30):22927–22932. [PubMed] [Google Scholar]
  75. Simeone A., Acampora D., Gulisano M., Stornaiuolo A., Boncinelli E. Nested expression domains of four homeobox genes in developing rostral brain. Nature. 1992 Aug 20;358(6388):687–690. doi: 10.1038/358687a0. [DOI] [PubMed] [Google Scholar]
  76. Smith D. R., Vogt P. K., Hayman M. J. The v-sea oncogene of avian erythroblastosis retrovirus S13: another member of the protein-tyrosine kinase gene family. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5291–5295. doi: 10.1073/pnas.86.14.5291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Sonnenberg E., Meyer D., Weidner K. M., Birchmeier C. Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. J Cell Biol. 1993 Oct;123(1):223–235. doi: 10.1083/jcb.123.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Sporn M. B., Roberts A. B. Transforming growth factor-beta: recent progress and new challenges. J Cell Biol. 1992 Dec;119(5):1017–1021. doi: 10.1083/jcb.119.5.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Stacker S. A., Hovens C. M., Vitali A., Pritchard M. A., Baker E., Sutherland G. R., Wilks A. F. Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK). Oncogene. 1993 May;8(5):1347–1356. [PubMed] [Google Scholar]
  80. Stanley E. R., Guilbert L. J., Tushinski R. J., Bartelmez S. H. CSF-1--a mononuclear phagocyte lineage-specific hemopoietic growth factor. J Cell Biochem. 1983;21(2):151–159. doi: 10.1002/jcb.240210206. [DOI] [PubMed] [Google Scholar]
  81. 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]
  82. 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]
  83. Takeshita K., Benz E. J. Gene expression during erythropoiesis. Int J Cell Cloning. 1991 Mar;9(2):109–122. doi: 10.1002/stem.5530090202. [DOI] [PubMed] [Google Scholar]
  84. Tamagnone L., Partanen J., Armstrong E., Lasota J., Ohgami K., Tazunoki T., LaForgia S., Huebner K., Alitalo K. The human ryk cDNA sequence predicts a protein containing two putative transmembrane segments and a tyrosine kinase catalytic domain. Oncogene. 1993 Jul;8(7):2009–2014. [PubMed] [Google Scholar]
  85. Vainchenker W., Bouguet J., Guichard J., Breton-Gorius J. Megakaryocyte colony formation from human bone marrow precursors. Blood. 1979 Oct;54(4):940–945. [PubMed] [Google Scholar]
  86. 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]
  87. 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]
  88. Williams D. E., Lyman S. D. Characterization of the gene-product of the Steel locus. Prog Growth Factor Res. 1991;3(4):235–242. doi: 10.1016/0955-2235(91)90002-l. [DOI] [PubMed] [Google Scholar]
  89. Yee K., Bishop T. R., Mather C., Zon L. I. Isolation of a novel receptor tyrosine kinase cDNA expressed by developing erythroid progenitors. Blood. 1993 Aug 15;82(4):1335–1343. [PubMed] [Google Scholar]
  90. Zarnegar R., DeFrances M. C., Kost D. P., Lindroos P., Michalopoulos G. K. Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy. Biochem Biophys Res Commun. 1991 May 31;177(1):559–565. doi: 10.1016/0006-291x(91)92020-k. [DOI] [PubMed] [Google Scholar]

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