Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1995 Nov 1;14(21):5288–5296. doi: 10.1002/j.1460-2075.1995.tb00213.x

Distinct signal transduction through the tyrosine-containing domains of the granulocyte colony-stimulating factor receptor.

A Yoshikawa 1, H Murakami 1, S Nagata 1
PMCID: PMC394638  PMID: 7489718

Abstract

The receptor for granulocyte colony-stimulating factor (G-CSFR) is a hemopoietic growth factor receptor, which mediates proliferation and differentiation signals. The cytoplasmic region of G-CSFR carries four tyrosine residues in its C-terminal half. We constructed mutant receptors in which each tyrosine residue of G-CSFR was mutated to phenylalanine. Two mutant receptors (Tyr703 and Tyr728) neither transduced the growth-inhibitory signal nor induced the neutrophil-specific myeloperoxidase (MPO) gene. The Tyr703 mutant did not induce morphological changes in cells, whereas transformants expressing the Tyr728 mutant adhered to plates with a macrophage-like morphology upon G-CSF stimulation. Mutation of the most distal tyrosine residue (Tyr763) abolished the ability of G-CSFR to stimulate the tyrosine phosphorylation of a cellular protein with an M(r) of 54 kDa. These results indicated that the regions around the three tyrosine residues of G-CSFR play essential and distinct roles in signal transduction.

Full text

PDF
5292

Images in this article

5289Image
on p.5289
5290Image
on p.5290
5292Image
on p.5292
5293Image
on p.5293
5293Image
on p.5293

Selected References

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

  1. Akira S., Nishio Y., Inoue M., Wang X. J., Wei S., Matsusaka T., Yoshida K., Sudo T., Naruto M., Kishimoto T. Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell. 1994 Apr 8;77(1):63–71. doi: 10.1016/0092-8674(94)90235-6. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bazan J. F. Haemopoietic receptors and helical cytokines. Immunol Today. 1990 Oct;11(10):350–354. doi: 10.1016/0167-5699(90)90139-z. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Cooper J. A., Esch F. S., Taylor S. S., Hunter T. Phosphorylation sites in enolase and lactate dehydrogenase utilized by tyrosine protein kinases in vivo and in vitro. J Biol Chem. 1984 Jun 25;259(12):7835–7841. [PubMed] [Google Scholar]
  6. Corey S. J., Burkhardt A. L., Bolen J. B., Geahlen R. L., Tkatch L. S., Tweardy D. J. Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4683–4687. doi: 10.1073/pnas.91.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
  8. Demetri G. D., Griffin J. D. Granulocyte colony-stimulating factor and its receptor. Blood. 1991 Dec 1;78(11):2791–2808. [PubMed] [Google Scholar]
  9. Dong F., van Buitenen C., Pouwels K., Hoefsloot L. H., Löwenberg B., Touw I. P. Distinct cytoplasmic regions of the human granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation. Mol Cell Biol. 1993 Dec;13(12):7774–7781. doi: 10.1128/mcb.13.12.7774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fukunaga R., Ishizaka-Ikeda E., Nagata S. Growth and differentiation signals mediated by different regions in the cytoplasmic domain of granulocyte colony-stimulating factor receptor. Cell. 1993 Sep 24;74(6):1079–1087. doi: 10.1016/0092-8674(93)90729-a. [DOI] [PubMed] [Google Scholar]
  11. Fukunaga R., Ishizaka-Ikeda E., Nagata S. Purification and characterization of the receptor for murine granulocyte colony-stimulating factor. J Biol Chem. 1990 Aug 15;265(23):14008–14015. [PubMed] [Google Scholar]
  12. Fukunaga R., Ishizaka-Ikeda E., Pan C. X., Seto Y., Nagata S. Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J. 1991 Oct;10(10):2855–2865. doi: 10.1002/j.1460-2075.1991.tb07835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fukunaga R., Ishizaka-Ikeda E., Seto Y., Nagata S. Expression cloning of a receptor for murine granulocyte colony-stimulating factor. Cell. 1990 Apr 20;61(2):341–350. doi: 10.1016/0092-8674(90)90814-u. [DOI] [PubMed] [Google Scholar]
  14. Fukunaga R., Seto Y., Mizushima S., Nagata S. Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8702–8706. doi: 10.1073/pnas.87.22.8702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heldin C. H. Dimerization of cell surface receptors in signal transduction. Cell. 1995 Jan 27;80(2):213–223. doi: 10.1016/0092-8674(95)90404-2. [DOI] [PubMed] [Google Scholar]
  16. Hilton D. J. LIF: lots of interesting functions. Trends Biochem Sci. 1992 Feb;17(2):72–76. doi: 10.1016/0968-0004(92)90505-4. [DOI] [PubMed] [Google Scholar]
  17. Ihle J. N., Kerr I. M. Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet. 1995 Feb;11(2):69–74. doi: 10.1016/s0168-9525(00)89000-9. [DOI] [PubMed] [Google Scholar]
  18. Ihle J. N., Witthuhn B. A., Quelle F. W., Yamamoto K., Thierfelder W. E., Kreider B., Silvennoinen O. Signaling by the cytokine receptor superfamily: JAKs and STATs. Trends Biochem Sci. 1994 May;19(5):222–227. doi: 10.1016/0968-0004(94)90026-4. [DOI] [PubMed] [Google Scholar]
  19. Ishizaka-Ikeda E., Fukunaga R., Wood W. I., Goeddel D. V., Nagata S. Signal transduction mediated by growth hormone receptor and its chimeric molecules with the granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):123–127. doi: 10.1073/pnas.90.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kishimoto T., Taga T., Akira S. Cytokine signal transduction. Cell. 1994 Jan 28;76(2):253–262. doi: 10.1016/0092-8674(94)90333-6. [DOI] [PubMed] [Google Scholar]
  21. Kishimoto T. The biology of interleukin-6. Blood. 1989 Jul;74(1):1–10. [PubMed] [Google Scholar]
  22. Larsen A., Davis T., Curtis B. M., Gimpel S., Sims J. E., Cosman D., Park L., Sorensen E., March C. J., Smith C. A. Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains. J Exp Med. 1990 Dec 1;172(6):1559–1570. doi: 10.1084/jem.172.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee K. H., Kinashi T., Tohyama K., Tashiro K., Funato N., Hama K., Honjo T. Different stromal cell lines support lineage-selective differentiation of the multipotential bone marrow stem cell clone LyD9. J Exp Med. 1991 May 1;173(5):1257–1266. doi: 10.1084/jem.173.5.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lieschke G. J., Grail D., Hodgson G., Metcalf D., Stanley E., Cheers C., Fowler K. J., Basu S., Zhan Y. F., Dunn A. R. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood. 1994 Sep 15;84(6):1737–1746. [PubMed] [Google Scholar]
  25. Marshall C. J. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995 Jan 27;80(2):179–185. doi: 10.1016/0092-8674(95)90401-8. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Mui A. L., Miyajima A. Cytokine receptors and signal transduction. Prog Growth Factor Res. 1994;5(1):15–35. doi: 10.1016/0955-2235(94)90015-9. [DOI] [PubMed] [Google Scholar]
  29. Nagata S., Fukunaga R. Granulocyte colony-stimulating factor and its receptor. Prog Growth Factor Res. 1991;3(2):131–141. doi: 10.1016/s0955-2235(05)80004-3. [DOI] [PubMed] [Google Scholar]
  30. Nicholson S. E., Oates A. C., Harpur A. G., Ziemiecki A., Wilks A. F., Layton J. E. Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2985–2988. doi: 10.1073/pnas.91.8.2985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pan C. X., Fukunaga R., Yonehara S., Nagata S. Unidirectional cross-phosphorylation between the granulocyte colony-stimulating factor and interleukin 3 receptors. J Biol Chem. 1993 Dec 5;268(34):25818–25823. [PubMed] [Google Scholar]
  32. Pawson T. Protein modules and signalling networks. Nature. 1995 Feb 16;373(6515):573–580. doi: 10.1038/373573a0. [DOI] [PubMed] [Google Scholar]
  33. Schlessinger J., Ullrich A. Growth factor signaling by receptor tyrosine kinases. Neuron. 1992 Sep;9(3):383–391. doi: 10.1016/0896-6273(92)90177-f. [DOI] [PubMed] [Google Scholar]
  34. Seldin D. C., Leder P. Mutational analysis of a critical signaling domain of the human interleukin 4 receptor. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2140–2144. doi: 10.1073/pnas.91.6.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shimoda K., Iwasaki H., Okamura S., Ohno Y., Kubota A., Arima F., Otsuka T., Niho Y. G-CSF induces tyrosine phosphorylation of the JAK2 protein in the human myeloid G-CSF responsive and proliferative cells, but not in mature neutrophils. Biochem Biophys Res Commun. 1994 Sep 15;203(2):922–928. doi: 10.1006/bbrc.1994.2270. [DOI] [PubMed] [Google Scholar]
  36. Shimoda K., Okamura S., Harada N., Ikematsu W., Kondo S., Kawasaki C., Tanaka T., Etou T., Akashi K., Okamura T. Granulocyte colony-stimulating factor receptors on human acute leukemia: biphenotypic leukemic cells possess granulocyte colony-stimulating factor receptors. Cancer Res. 1992 Jun 1;52(11):3052–3055. [PubMed] [Google Scholar]
  37. Songyang Z., Carraway K. L., 3rd, Eck M. J., Harrison S. C., Feldman R. A., Mohammadi M., Schlessinger J., Hubbard S. R., Smith D. P., Eng C. Catalytic specificity of protein-tyrosine kinases is critical for selective signalling. Nature. 1995 Feb 9;373(6514):536–539. doi: 10.1038/373536a0. [DOI] [PubMed] [Google Scholar]
  38. Stahl N., Farruggella T. J., Boulton T. G., Zhong Z., Darnell J. E., Jr, Yancopoulos G. D. Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science. 1995 Mar 3;267(5202):1349–1353. doi: 10.1126/science.7871433. [DOI] [PubMed] [Google Scholar]
  39. Tian S. S., Lamb P., Seidel H. M., Stein R. B., Rosen J. Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Blood. 1994 Sep 15;84(6):1760–1764. [PubMed] [Google Scholar]
  40. Tsuchiya M., Asano S., Kaziro Y., Nagata S. Isolation and characterization of the cDNA for murine granulocyte colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7633–7637. doi: 10.1073/pnas.83.20.7633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Uetsuki T., Naito A., Nagata S., Kaziro Y. Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha. J Biol Chem. 1989 Apr 5;264(10):5791–5798. [PubMed] [Google Scholar]
  42. Venturelli D., Shirsat N., Gemperlein I., Bittenbender S., Hudson S., Rovera G. Nucleotide sequence of cDNA for murine myeloperoxidase. Nucleic Acids Res. 1989 Jul 25;17(14):5852–5852. doi: 10.1093/nar/17.14.5852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Ziegler S. F., Bird T. A., Morella K. K., Mosley B., Gearing D. P., Baumann H. Distinct regions of the human granulocyte-colony-stimulating factor receptor cytoplasmic domain are required for proliferation and gene induction. Mol Cell Biol. 1993 Apr;13(4):2384–2390. doi: 10.1128/mcb.13.4.2384. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES