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. 1993 Nov;12(11):4181–4189. doi: 10.1002/j.1460-2075.1993.tb06102.x

Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signaling.

N Sato 1, K Sakamaki 1, N Terada 1, K Arai 1, A Miyajima 1
PMCID: PMC413712  PMID: 8223433

Abstract

The high-affinity receptors for granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3) and IL-5 consist of two subunits, alpha and beta. The alpha subunits are specific to each cytokine and the same beta subunit (beta c) is shared by these three receptors. Although none of these receptor subunits has intrinsic kinase activity, these cytokines induce protein tyrosine phosphorylation, activation of Ras, Raf-1 and MAP kinase, and transcriptional activation of nuclear proto-oncogenes such as c-myc, c-fos and c-jun. In this paper, we describe a detailed analysis of the signaling potential of the beta c subunit by using a series of cytoplasmic deletion mutants. The human beta c consists of 881 amino acid residues. A C-terminal deletion mutant of beta c at amino acid 763 (beta 763) induced phosphorylation of Shc and activation of Ras, Raf-1, MAP kinase and p70 S6 kinase, whereas a deletion at amino acid 626 (beta 626) induced none of these effects. The beta 763 mutant, as well as the full-length beta c, induced transcription of c-myc, c-fos and c-jun. Deletions at amino acid 517 (beta 517) and 626 (beta 626) induced c-myc and pim-1, but no induction of c-fos and c-jun was observed. GM-CSF increased phosphatidylinositol 3 kinase (PI3-K) activity in anti-phosphotyrosine immunoprecipitates from cells expressing beta 763 as well as beta c, whereas it was only marginally increased from cells expressing beta 517 or beta 626. Thus, there are at least two distinct regions within the cytoplasmic domain of beta c that are responsible for different signals, i.e. a membrane proximal region of approximately 60 amino acid residues upstream of Glu517 is essential for induction of c-myc and pim-1, and a distal region of approximately 140 amino acid residues (between Leu626 and Ser763) is required for activation of Ras, Raf-1, MAP kinase and p70 S6 kinase, as well as induction of c-fos and c-jun.

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Selected References

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

  1. Arai K. I., Lee F., Miyajima A., Miyatake S., Arai N., Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836. doi: 10.1146/annurev.bi.59.070190.004031. [DOI] [PubMed] [Google Scholar]
  2. Askew D. S., Ashmun R. A., Simmons B. C., Cleveland J. L. Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene. 1991 Oct;6(10):1915–1922. [PubMed] [Google Scholar]
  3. Ballou L. M., Luther H., Thomas G. MAP2 kinase and 70K S6 kinase lie on distinct signalling pathways. Nature. 1991 Jan 24;349(6307):348–350. doi: 10.1038/349348a0. [DOI] [PubMed] [Google Scholar]
  4. Bar-Sagi D., Feramisco J. R. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985 Oct;42(3):841–848. doi: 10.1016/0092-8674(85)90280-6. [DOI] [PubMed] [Google Scholar]
  5. Berns A. Tumorigenesis in transgenic mice: identification and characterization of synergizing oncogenes. J Cell Biochem. 1991 Oct;47(2):130–135. doi: 10.1002/jcb.240470206. [DOI] [PubMed] [Google Scholar]
  6. Blenis J., Chung J., Erikson E., Alcorta D. A., Erikson R. L. Distinct mechanisms for the activation of the RSK kinases/MAP2 kinase/pp90rsk and pp70-S6 kinase signaling systems are indicated by inhibition of protein synthesis. Cell Growth Differ. 1991 Jun;2(6):279–285. [PubMed] [Google Scholar]
  7. Blenis J. Growth-regulated signal transduction by the MAP kinases and RSKs. Cancer Cells. 1991 Nov;3(11):445–449. [PubMed] [Google Scholar]
  8. 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]
  9. Carroll M. P., Clark-Lewis I., Rapp U. R., May W. S. Interleukin-3 and granulocyte-macrophage colony-stimulating factor mediate rapid phosphorylation and activation of cytosolic c-raf. J Biol Chem. 1990 Nov 15;265(32):19812–19817. [PubMed] [Google Scholar]
  10. Carroll M. P., Spivak J. L., McMahon M., Weich N., Rapp U. R., May W. S. Erythropoietin induces Raf-1 activation and Raf-1 is required for erythropoietin-mediated proliferation. J Biol Chem. 1991 Aug 15;266(23):14964–14969. [PubMed] [Google Scholar]
  11. 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]
  12. Cleveland J. L., Dean M., Rosenberg N., Wang J. Y., Rapp U. R. Tyrosine kinase oncogenes abrogate interleukin-3 dependence of murine myeloid cells through signaling pathways involving c-myc: conditional regulation of c-myc transcription by temperature-sensitive v-abl. Mol Cell Biol. 1989 Dec;9(12):5685–5695. doi: 10.1128/mcb.9.12.5685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Conscience J. F., Verrier B., Martin G. Interleukin-3-dependent expression of the c-myc and c-fos proto-oncogenes in hemopoietic cell lines. EMBO J. 1986 Feb;5(2):317–323. doi: 10.1002/j.1460-2075.1986.tb04215.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Duronio V., Welham M. J., Abraham S., Dryden P., Schrader J. W. p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1587–1591. doi: 10.1073/pnas.89.5.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Escobedo J. A., Navankasattusas S., Kavanaugh W. M., Milfay D., Fried V. A., Williams L. T. cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor. Cell. 1991 Apr 5;65(1):75–82. doi: 10.1016/0092-8674(91)90409-r. [DOI] [PubMed] [Google Scholar]
  16. Gasson J. C. Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood. 1991 Mar 15;77(6):1131–1145. [PubMed] [Google Scholar]
  17. Gearing D. P., King J. A., Gough N. M., Nicola N. A. Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. EMBO J. 1989 Dec 1;8(12):3667–3676. doi: 10.1002/j.1460-2075.1989.tb08541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gille H., Sharrocks A. D., Shaw P. E. Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature. 1992 Jul 30;358(6385):414–417. doi: 10.1038/358414a0. [DOI] [PubMed] [Google Scholar]
  19. Gotoh Y., Nishida E., Sakai H. Okadaic acid activates microtubule-associated protein kinase in quiescent fibroblastic cells. Eur J Biochem. 1990 Nov 13;193(3):671–674. doi: 10.1111/j.1432-1033.1990.tb19385.x. [DOI] [PubMed] [Google Scholar]
  20. Hara T., Miyajima A. Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3). EMBO J. 1992 May;11(5):1875–1884. doi: 10.1002/j.1460-2075.1992.tb05239.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hayashida K., Kitamura T., Gorman D. M., Arai K., Yokota T., Miyajima A. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9655–9659. doi: 10.1073/pnas.87.24.9655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Herschman H. R. Primary response genes induced by growth factors and tumor promoters. Annu Rev Biochem. 1991;60:281–319. doi: 10.1146/annurev.bi.60.070191.001433. [DOI] [PubMed] [Google Scholar]
  23. Hu P., Margolis B., Skolnik E. Y., Lammers R., Ullrich A., Schlessinger J. Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. Mol Cell Biol. 1992 Mar;12(3):981–990. doi: 10.1128/mcb.12.3.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hume C. R., Nocka K. H., Sorrentino V., Lee J. S., Fleissner E. Constitutive c-myc expression enhances the response of murine mast cells to IL-3, but does not eliminate their requirement for growth factors. Oncogene. 1988 Mar;2(3):223–226. [PubMed] [Google Scholar]
  25. Ihle J. N. Interleukin-3 and hematopoiesis. Chem Immunol. 1992;51:65–106. doi: 10.1159/000420755. [DOI] [PubMed] [Google Scholar]
  26. Isfort R. J., Ihle J. N. Multiple hematopoietic growth factors signal through tyrosine phosphorylation. Growth Factors. 1990;2(2-3):213–220. doi: 10.3109/08977199009071507. [DOI] [PubMed] [Google Scholar]
  27. Kanakura Y., Druker B., Cannistra S. A., Furukawa Y., Torimoto Y., Griffin J. D. Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins. Blood. 1990 Aug 15;76(4):706–715. [PubMed] [Google Scholar]
  28. Kitamura T., Hayashida K., Sakamaki K., Yokota T., Arai K., Miyajima A. Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5082–5086. doi: 10.1073/pnas.88.12.5082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kitamura T., Miyajima A. Functional reconstitution of the human interleukin-3 receptor. Blood. 1992 Jul 1;80(1):84–90. [PubMed] [Google Scholar]
  30. Kitamura T., Sato N., Arai K., Miyajima A. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors. Cell. 1991 Sep 20;66(6):1165–1174. doi: 10.1016/0092-8674(91)90039-2. [DOI] [PubMed] [Google Scholar]
  31. Krystal G., Alai M., Cutler R. L., Dickeson H., Mui A. L., Wognum A. W. Hematopoietic growth factor receptors. Hematol Pathol. 1991;5(4):141–162. [PubMed] [Google Scholar]
  32. Kuo C. J., Chung J., Fiorentino D. F., Flanagan W. M., Blenis J., Crabtree G. R. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature. 1992 Jul 2;358(6381):70–73. doi: 10.1038/358070a0. [DOI] [PubMed] [Google Scholar]
  33. Lilly M., Le T., Holland P., Hendrickson S. L. Sustained expression of the pim-1 kinase is specifically induced in myeloid cells by cytokines whose receptors are structurally related. Oncogene. 1992 Apr;7(4):727–732. [PubMed] [Google Scholar]
  34. Lopez A. F., Vadas M. A., Woodcock J. M., Milton S. E., Lewis A., Elliott M. J., Gillis D., Ireland R., Olwell E., Park L. S. Interleukin-5, interleukin-3, and granulocyte-macrophage colony-stimulating factor cross-compete for binding to cell surface receptors on human eosinophils. J Biol Chem. 1991 Dec 25;266(36):24741–24747. [PubMed] [Google Scholar]
  35. Merida I., Diez E., Gaulton G. N. IL-2 binding activates a tyrosine-phosphorylated phosphatidylinositol-3-kinase. J Immunol. 1991 Oct 1;147(7):2202–2207. [PubMed] [Google Scholar]
  36. Metcalf D. Hemopoietic regulators. Trends Biochem Sci. 1992 Aug;17(8):286–289. doi: 10.1016/0968-0004(92)90436-d. [DOI] [PubMed] [Google Scholar]
  37. Minami Y., Kono T., Yamada K., Kobayashi N., Kawahara A., Perlmutter R. M., Taniguchi T. Association of p56lck with IL-2 receptor beta chain is critical for the IL-2-induced activation of p56lck. EMBO J. 1993 Feb;12(2):759–768. doi: 10.1002/j.1460-2075.1993.tb05710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Miyajima A., Hara T., Kitamura T. Common subunits of cytokine receptors and the functional redundancy of cytokines. Trends Biochem Sci. 1992 Oct;17(10):378–382. doi: 10.1016/0968-0004(92)90004-s. [DOI] [PubMed] [Google Scholar]
  39. Miyajima A., Kitamura T., Harada N., Yokota T., Arai K. Cytokine receptors and signal transduction. Annu Rev Immunol. 1992;10:295–331. doi: 10.1146/annurev.iy.10.040192.001455. [DOI] [PubMed] [Google Scholar]
  40. Miyajima A., Schreurs J., Otsu K., Kondo A., Arai K., Maeda S. Use of the silkworm, Bombyx mori, and an insect baculovirus vector for high-level expression and secretion of biologically active mouse interleukin-3. Gene. 1987;58(2-3):273–281. doi: 10.1016/0378-1119(87)90382-9. [DOI] [PubMed] [Google Scholar]
  41. Morla A. O., Schreurs J., Miyajima A., Wang J. Y. Hematopoietic growth factors activate the tyrosine phosphorylation of distinct sets of proteins in interleukin-3-dependent murine cell lines. Mol Cell Biol. 1988 May;8(5):2214–2218. doi: 10.1128/mcb.8.5.2214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Murata Y., Yamaguchi N., Hitoshi Y., Tominaga A., Takatsu K. Interleukin 5 and interleukin 3 induce serine and tyrosine phosphorylations of several cellular proteins in an interleukin 5-dependent cell line. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1102–1108. doi: 10.1016/s0006-291x(05)80899-x. [DOI] [PubMed] [Google Scholar]
  43. Nakanishi H., Brewer K. A., Exton J. H. Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1993 Jan 5;268(1):13–16. [PubMed] [Google Scholar]
  44. Nicola N. A., Metcalf D. Subunit promiscuity among hemopoietic growth factor receptors. Cell. 1991 Oct 4;67(1):1–4. doi: 10.1016/0092-8674(91)90564-f. [DOI] [PubMed] [Google Scholar]
  45. Noda M., Ko M., Ogura A., Liu D. G., Amano T., Takano T., Ikawa Y. Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature. 1985 Nov 7;318(6041):73–75. doi: 10.1038/318073a0. [DOI] [PubMed] [Google Scholar]
  46. Okuda K., Sanghera J. S., Pelech S. L., Kanakura Y., Hallek M., Griffin J. D., Druker B. J. Granulocyte-macrophage colony-stimulating factor, interleukin-3, and steel factor induce rapid tyrosine phosphorylation of p42 and p44 MAP kinase. Blood. 1992 Jun 1;79(11):2880–2887. [PubMed] [Google Scholar]
  47. Palacios R., Steinmetz M. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 1985 Jul;41(3):727–734. doi: 10.1016/s0092-8674(85)80053-2. [DOI] [PubMed] [Google Scholar]
  48. Park L. S., Martin U., Sorensen R., Luhr S., Morrissey P. J., Cosman D., Larsen A. Cloning of the low-affinity murine granulocyte-macrophage colony-stimulating factor receptor and reconstitution of a high-affinity receptor complex. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4295–4299. doi: 10.1073/pnas.89.10.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Pazin M. J., Williams L. T. Triggering signaling cascades by receptor tyrosine kinases. Trends Biochem Sci. 1992 Oct;17(10):374–378. doi: 10.1016/0968-0004(92)90003-r. [DOI] [PubMed] [Google Scholar]
  50. Pelicci G., Lanfrancone L., Grignani F., McGlade J., Cavallo F., Forni G., Nicoletti I., Grignani F., Pawson T., Pelicci P. G. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. Cell. 1992 Jul 10;70(1):93–104. doi: 10.1016/0092-8674(92)90536-l. [DOI] [PubMed] [Google Scholar]
  51. Rapp U. R., Troppmair J., Carroll M., May S. Role of raf-1 protein kinase in IL-3 and GM-CSF-mediated signal transduction. Curr Top Microbiol Immunol. 1990;166:129–139. doi: 10.1007/978-3-642-75889-8_17. [DOI] [PubMed] [Google Scholar]
  52. Roussel M. F., Cleveland J. L., Shurtleff S. A., Sherr C. J. Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling. Nature. 1991 Sep 26;353(6342):361–363. doi: 10.1038/353361a0. [DOI] [PubMed] [Google Scholar]
  53. Sakamaki K., Miyajima I., Kitamura T., Miyajima A. Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation. EMBO J. 1992 Oct;11(10):3541–3549. doi: 10.1002/j.1460-2075.1992.tb05437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Satoh T., Endo M., Nakafuku M., Nakamura S., Kaziro Y. Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5993–5997. doi: 10.1073/pnas.87.15.5993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Satoh T., Minami Y., Kono T., Yamada K., Kawahara A., Taniguchi T., Kaziro Y. Interleukin 2-induced activation of Ras requires two domains of interleukin 2 receptor beta subunit, the essential region for growth stimulation and Lck-binding domain. J Biol Chem. 1992 Dec 15;267(35):25423–25427. [PubMed] [Google Scholar]
  56. Satoh T., Nakafuku M., Kaziro Y. Function of Ras as a molecular switch in signal transduction. J Biol Chem. 1992 Dec 5;267(34):24149–24152. [PubMed] [Google Scholar]
  57. Satoh T., Nakafuku M., Miyajima A., Kaziro Y. Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and granulocyte/macrophage colony-stimulating factor, but not from interleukin 4. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3314–3318. doi: 10.1073/pnas.88.8.3314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Satoh T., Uehara Y., Kaziro Y. Inhibition of interleukin 3 and granulocyte-macrophage colony-stimulating factor stimulated increase of active ras.GTP by herbimycin A, a specific inhibitor of tyrosine kinases. J Biol Chem. 1992 Feb 5;267(4):2537–2541. [PubMed] [Google Scholar]
  59. Shanafelt A. B., Miyajima A., Kitamura T., Kastelein R. A. The amino-terminal helix of GM-CSF and IL-5 governs high affinity binding to their receptors. EMBO J. 1991 Dec;10(13):4105–4112. doi: 10.1002/j.1460-2075.1991.tb04987.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Shibuya H., Yoneyama M., Ninomiya-Tsuji J., Matsumoto K., Taniguchi T. IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc. Cell. 1992 Jul 10;70(1):57–67. doi: 10.1016/0092-8674(92)90533-i. [DOI] [PubMed] [Google Scholar]
  61. Takaki S., Mita S., Kitamura T., Yonehara S., Yamaguchi N., Tominaga A., Miyajima A., Takatsu K. Identification of the second subunit of the murine interleukin-5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor. EMBO J. 1991 Oct;10(10):2833–2838. doi: 10.1002/j.1460-2075.1991.tb07832.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Takaki S., Murata Y., Kitamura T., Miyajima A., Tominaga A., Takatsu K. Reconstitution of the functional receptors for murine and human interleukin 5. J Exp Med. 1993 Jun 1;177(6):1523–1529. doi: 10.1084/jem.177.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Takaki S., Tominaga A., Hitoshi Y., Mita S., Sonoda E., Yamaguchi N., Takatsu K. Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J. 1990 Dec;9(13):4367–4374. doi: 10.1002/j.1460-2075.1990.tb07886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Takatsu K., Tominaga A. Interleukin 5 and its receptor. Prog Growth Factor Res. 1991;3(2):87–102. doi: 10.1016/s0955-2235(05)80001-8. [DOI] [PubMed] [Google Scholar]
  65. Tavernier J., Devos R., Cornelis S., Tuypens T., Van der Heyden J., Fiers W., Plaetinck G. A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF. Cell. 1991 Sep 20;66(6):1175–1184. doi: 10.1016/0092-8674(91)90040-6. [DOI] [PubMed] [Google Scholar]
  66. Terada N., Franklin R. A., Lucas J. J., Blenis J., Gelfand E. W. Failure of rapamycin to block proliferation once resting cells have entered the cell cycle despite inactivation of p70 S6 kinase. J Biol Chem. 1993 Jun 5;268(16):12062–12068. [PubMed] [Google Scholar]
  67. Wang L. M., Keegan A. D., Paul W. E., Heidaran M. A., Gutkind J. S., Pierce J. H. IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells. EMBO J. 1992 Dec;11(13):4899–4908. doi: 10.1002/j.1460-2075.1992.tb05596.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Watanabe S., Mui A. L., Muto A., Chen J. X., Hayashida K., Yokota T., Miyajima A., Arai K. Reconstituted human granulocyte-macrophage colony-stimulating factor receptor transduces growth-promoting signals in mouse NIH 3T3 cells: comparison with signalling in BA/F3 pro-B cells. Mol Cell Biol. 1993 Mar;13(3):1440–1448. doi: 10.1128/mcb.13.3.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Welham M. J., Duronio V., Sanghera J. S., Pelech S. L., Schrader J. W. Multiple hemopoietic growth factors stimulate activation of mitogen-activated protein kinase family members. J Immunol. 1992 Sep 1;149(5):1683–1693. [PubMed] [Google Scholar]
  70. van Lohuizen M., Verbeek S., Scheijen B., Wientjens E., van der Gulden H., Berns A. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991 May 31;65(5):737–752. doi: 10.1016/0092-8674(91)90382-9. [DOI] [PubMed] [Google Scholar]

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