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. 1988 Aug;85(16):5903–5907. doi: 10.1073/pnas.85.16.5903

Colony-stimulating factor 1-mediated regulation of a chimeric c-fms/v-fms receptor containing the v-fms-encoded tyrosine kinase domain.

M F Roussel 1, J R Downing 1, R A Ashmun 1, C W Rettenmier 1, C J Sherr 1
PMCID: PMC281873  PMID: 2842754

Abstract

A chimeric gene specifying the 308 N-terminal amino acids of the extracellular ligand binding domain of the human c-fms protooncogene joined to the remainder of the feline v-fms oncogene product encodes a functional colony-stimulating factor 1 (CSF-1) receptor. When expressed in mouse NIH 3T3 fibroblasts, the chimeric gene product was rapidly transported to the cell surface, was autophosphorylated on tyrosine only in response to human recombinant CSF-1, underwent ligand-induced but not phorbol ester-induced down-modulation, and stimulated CSF-1-dependent cell proliferation. By contrast, the C-terminally truncated glycoprotein encoded by the v-fms oncogene is partially inhibited in its transport to the plasma membrane, is constitutively phosphorylated on tyrosine, and is relatively refractory to both ligand-induced and phorbol ester-induced down-modulation. Although the v-fms oncogene can transform cells in the absence of CSF-1, its tyrosine kinase activity and turnover can be appropriately regulated by the human c-fms-encoded ligand binding domain. The results confirm that C-terminal truncation of the c-fms gene is insufficient to activate its transforming potential and suggest that an additional mutation in its distal extracellular domain is required for oncogenic activation.

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Selected References

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

  1. Anderson S. J., Furth M., Wolff L., Ruscetti S. K., Sherr C. J. Monoclonal antibodies to the transformation-specific glycoprotein encoded by the feline retroviral oncogene v-fms. J Virol. 1982 Nov;44(2):696–702. doi: 10.1128/jvi.44.2.696-702.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson S. J., Gonda M. A., Rettenmier C. W., Sherr C. J. Subcellular localization of glycoproteins encoded by the viral oncogene v-fms. J Virol. 1984 Sep;51(3):730–741. doi: 10.1128/jvi.51.3.730-741.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bravo R., Neuberg M., Burckhardt J., Almendral J., Wallich R., Müller R. Involvement of common and cell type-specific pathways in c-fos gene control: stable induction of cAMP in macrophages. Cell. 1987 Jan 30;48(2):251–260. doi: 10.1016/0092-8674(87)90428-4. [DOI] [PubMed] [Google Scholar]
  4. Carroll D., Ajioka R. S., Georgopoulos C. Bacteriophage lambda cloning vehicles for studies of genetic recombination. Gene. 1980 Aug;10(3):261–271. doi: 10.1016/0378-1119(80)90055-4. [DOI] [PubMed] [Google Scholar]
  5. Chen B. D., Lin H. S., Hsu S. Tumor-promoting phorbol esters inhibit the binding of colony-stimulating factor (CSF-1) to murine peritoneal exudate macrophages. J Cell Physiol. 1983 Aug;116(2):207–212. doi: 10.1002/jcp.1041160212. [DOI] [PubMed] [Google Scholar]
  6. Coussens L., Van Beveren C., Smith D., Chen E., Mitchell R. L., Isacke C. M., Verma I. M., Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. doi: 10.1038/320277a0. [DOI] [PubMed] [Google Scholar]
  7. Crouse G. F., McEwan R. N., Pearson M. L. Expression and amplification of engineered mouse dihydrofolate reductase minigenes. Mol Cell Biol. 1983 Feb;3(2):257–266. doi: 10.1128/mcb.3.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Di Fiore P. P., Pierce J. H., Fleming T. P., Hazan R., Ullrich A., King C. R., Schlessinger J., Aaronson S. A. Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. Cell. 1987 Dec 24;51(6):1063–1070. doi: 10.1016/0092-8674(87)90592-7. [DOI] [PubMed] [Google Scholar]
  9. Downing J. R., Rettenmier C. W., Sherr C. J. Ligand-induced tyrosine kinase activity of the colony-stimulating factor 1 receptor in a murine macrophage cell line. Mol Cell Biol. 1988 Apr;8(4):1795–1799. doi: 10.1128/mcb.8.4.1795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ek B., Westermark B., Wasteson A., Heldin C. H. Stimulation of tyrosine-specific phosphorylation by platelet-derived growth factor. Nature. 1982 Feb 4;295(5848):419–420. doi: 10.1038/295419a0. [DOI] [PubMed] [Google Scholar]
  11. Ellis L., Morgan D. O., Jong S. M., Wang L. H., Roth R. A., Rutter W. J. Heterologous transmembrane signaling by a human insulin receptor-v-ros hybrid in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5101–5105. doi: 10.1073/pnas.84.15.5101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Furman W. L., Rettenmier C. W., Chen J. H., Roussel M. F., Quinn C. O., Sherr C. J. Antibodies to distal carboxyl terminal epitopes in the v-fms-coded glycoprotein do not cross-react with the c-fms gene product. Virology. 1986 Jul 30;152(2):432–445. doi: 10.1016/0042-6822(86)90145-5. [DOI] [PubMed] [Google Scholar]
  13. Guilbert L. J., Stanley E. R. The interaction of 125I-colony-stimulating factor-1 with bone marrow-derived macrophages. J Biol Chem. 1986 Mar 25;261(9):4024–4032. [PubMed] [Google Scholar]
  14. Hampe A., Gobet M., Sherr C. J., Galibert F. Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. Proc Natl Acad Sci U S A. 1984 Jan;81(1):85–89. doi: 10.1073/pnas.81.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heard J. M., Roussel M. F., Rettenmier C. W., Sherr C. J. Multilineage hematopoietic disorders induced by transplantation of bone marrow cells expressing the v-fms oncogene. Cell. 1987 Nov 20;51(4):663–673. doi: 10.1016/0092-8674(87)90135-8. [DOI] [PubMed] [Google Scholar]
  16. Honegger A. M., Dull T. J., Felder S., Van Obberghen E., Bellot F., Szapary D., Schmidt A., Ullrich A., Schlessinger J. Point mutation at the ATP binding site of EGF receptor abolishes protein-tyrosine kinase activity and alters cellular routing. Cell. 1987 Oct 23;51(2):199–209. doi: 10.1016/0092-8674(87)90147-4. [DOI] [PubMed] [Google Scholar]
  17. Jacobs S., Kull F. C., Jr, Earp H. S., Svoboda M. E., Van Wyk J. J., Cuatrecasas P. Somatomedin-C stimulates the phosphorylation of the beta-subunit of its own receptor. J Biol Chem. 1983 Aug 25;258(16):9581–9584. [PubMed] [Google Scholar]
  18. Kasuga M., Zick Y., Blithe D. L., Crettaz M., Kahn C. R. Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system. Nature. 1982 Aug 12;298(5875):667–669. doi: 10.1038/298667a0. [DOI] [PubMed] [Google Scholar]
  19. McDonough S. K., Larsen S., Brodey R. S., Stock N. D., Hardy W. D., Jr A transmissible feline fibrosarcoma of viral origin. Cancer Res. 1971 Jul;31(7):953–956. [PubMed] [Google Scholar]
  20. Miller A. D., Buttimore C. Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus production. Mol Cell Biol. 1986 Aug;6(8):2895–2902. doi: 10.1128/mcb.6.8.2895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morrison D. K., Browning P. J., White M. F., Roberts T. M. Tyrosine phosphorylations in vivo associated with v-fms transformation. Mol Cell Biol. 1988 Jan;8(1):176–185. doi: 10.1128/mcb.8.1.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Müller R., Curran T., Müller D., Guilbert L. Induction of c-fos during myelomonocytic differentiation and macrophage proliferation. Nature. 1985 Apr 11;314(6011):546–548. doi: 10.1038/314546a0. [DOI] [PubMed] [Google Scholar]
  23. Nishimura J., Huang J. S., Deuel T. F. Platelet-derived growth factor stimulates tyrosine-specific protein kinase activity in Swiss mouse 3T3 cell membranes. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4303–4307. doi: 10.1073/pnas.79.14.4303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Orlofsky A., Stanley E. R. CSF-1-induced gene expression in macrophages: dissociation from the mitogenic response. EMBO J. 1987 Oct;6(10):2947–2952. doi: 10.1002/j.1460-2075.1987.tb02599.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rettenmier C. W., Chen J. H., Roussel M. F., Sherr C. J. The product of the c-fms proto-oncogene: a glycoprotein with associated tyrosine kinase activity. Science. 1985 Apr 19;228(4697):320–322. doi: 10.1126/science.2580348. [DOI] [PubMed] [Google Scholar]
  26. Riedel H., Schlessinger J., Ullrich A. A chimeric, ligand-binding v-erbB/EGF receptor retains transforming potential. Science. 1987 Apr 10;236(4798):197–200. doi: 10.1126/science.3494307. [DOI] [PubMed] [Google Scholar]
  27. Roussel M. F., Dull T. J., Rettenmier C. W., Ralph P., Ullrich A., Sherr C. J. Transforming potential of the c-fms proto-oncogene (CSF-1 receptor). Nature. 1987 Feb 5;325(6104):549–552. doi: 10.1038/325549a0. [DOI] [PubMed] [Google Scholar]
  28. Roussel M. F., Rettenmier C. W., Look A. T., Sherr C. J. Cell surface expression of v-fms-coded glycoproteins is required for transformation. Mol Cell Biol. 1984 Oct;4(10):1999–2009. doi: 10.1128/mcb.4.10.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sacca R., Stanley E. R., Sherr C. J., Rettenmier C. W. Specific binding of the mononuclear phagocyte colony-stimulating factor CSF-1 to the product of the v-fms oncogene. Proc Natl Acad Sci U S A. 1986 May;83(10):3331–3335. doi: 10.1073/pnas.83.10.3331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  31. Tamura T., Simon E., Niemann H., Snoek G. T., Bauer H. gp140v-fms molecules expressed at the surface of cells transformed by the McDonough strain of feline sarcoma virus are phosphorylated in tyrosine and serine. Mol Cell Biol. 1986 Dec;6(12):4745–4748. doi: 10.1128/mcb.6.12.4745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tushinski R. J., Stanley E. R. The regulation of macrophage protein turnover by a colony stimulating factor (CSF-1). J Cell Physiol. 1983 Jul;116(1):67–75. doi: 10.1002/jcp.1041160111. [DOI] [PubMed] [Google Scholar]
  33. Tushinski R. J., Stanley E. R. The regulation of mononuclear phagocyte entry into S phase by the colony stimulating factor CSF-1. J Cell Physiol. 1985 Feb;122(2):221–228. doi: 10.1002/jcp.1041220210. [DOI] [PubMed] [Google Scholar]
  34. Ushiro H., Cohen S. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J Biol Chem. 1980 Sep 25;255(18):8363–8365. [PubMed] [Google Scholar]
  35. Velu T. J., Beguinot L., Vass W. C., Willingham M. C., Merlino G. T., Pastan I., Lowy D. R. Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene. Science. 1987 Dec 4;238(4832):1408–1410. doi: 10.1126/science.3500513. [DOI] [PubMed] [Google Scholar]
  36. Wheeler E. F., Askew D., May S., Ihle J. N., Sherr C. J. The v-fms oncogene induces factor-independent growth and transformation of the interleukin-3-dependent myeloid cell line FDC-P1. Mol Cell Biol. 1987 May;7(5):1673–1680. doi: 10.1128/mcb.7.5.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wheeler E. F., Rettenmier C. W., Look A. T., Sherr C. J. The v-fms oncogene induces factor independence and tumorigenicity in CSF-1 dependent macrophage cell line. 1986 Nov 27-Dec 3Nature. 324(6095):377–380. doi: 10.1038/324377a0. [DOI] [PubMed] [Google Scholar]
  38. Wheeler E. F., Roussel M. F., Hampe A., Walker M. H., Fried V. A., Look A. T., Rettenmier C. W., Sherr C. J. The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences. J Virol. 1986 Aug;59(2):224–233. doi: 10.1128/jvi.59.2.224-233.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yeung Y. G., Jubinsky P. T., Sengupta A., Yeung D. C., Stanley E. R. Purification of the colony-stimulating factor 1 receptor and demonstration of its tyrosine kinase activity. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1268–1271. doi: 10.1073/pnas.84.5.1268. [DOI] [PMC free article] [PubMed] [Google Scholar]

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