Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

The fibroblast growth factor receptor FGFR-4 acts as a ligand dependent modulator of erythroid cell proliferation

Abstract

Receptor and non-receptor tyrosine kinases constitute a large family of proteins that play a pivotal role in hematopoiesis. Here we conducted a comprehensive survey of tyrosine kinase gene expression in primary erythroid progenitor cells from bone marrow by employing a PCR-based strategy that targets the conserved kinase encoding region. We demonstrate that erythroid progenitor cells express several receptor and non-receptor tyrosine kinases, like c-kit, Jak1, Ryk, FAK, Syk, Arg, Csk and members of the insulin receptor family. Specific changes in the expression profile of tyrosine kinases were observed following differentiation induction. We also report on the identification of a new ligand dependent modulator of erythropoiesis, fibroblast growth factor receptor-4 (FGFR-4). FGFR-4 is effectively expressed in erythroid progenitors and downregulated when cells differentiate. Furthermore, the FGFR-4 ligand, basic fibroblast growth factor (bFGF), enhanced erythroid cell proliferation induced by SCF or insulin, and thus modulated both erythroid proliferation and differentiation in vitro.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 3
Figure 2
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Armstrong E, Vainikka S, Partanen J, Korhonen J and Alitalo R. . 1992 Cancer Res. 52: 2004–2007.

  • Bartunek P, Karafiat V, Dvorakova M, Mandikova S, Zahorova V, Zenke M and Dvorak M. . 1997 Oncogene 15: 2939–2949.

  • Bartunek P, Pichlikova L, Stengl G, Boehmelt G, Martin FH, Beug H, Dvorak M and Zenke M. . 1996 Cytokine 8: 14–20.

  • Beug H, Steinlein P, Bartunek P and Hayman MJ. . 1995 Methods Enzymol. 254: 41–76.

  • Briegel K, Bartunek P, Stengl G, Lim KC, Beug H, Engel JD and Zenke M. . 1996 Development 122: 3839–3850.

  • Briegel K, Lim KC, Plank C, Beug H, Engel JD and Zenke M. . 1993 Genes Dev. 7: 1097–1109.

  • Broudy VC. . 1997 Blood 90: 1345–1364.

  • Choi K, Kennedy M and Keller G. . 1993 Proc. Natl. Acad. Sci. USA 90: 5747–5751.

  • Choi K, Wall C, Hanratty R and Keller G. . 1994 Oncogene 9: 1261–1266.

  • Chomczynski P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Coulier F, Pontarotti P, Roubin R, Hartung H, Goldfarb M and Birnbaum D. . 1997 J. Mol. Evol. 44: 43–56.

  • Coussens L, Van Beveren C, Smith D, Chen E, Mitchell RL, Isacke CM, Verma IM and Ullrich A. . 1986 Nature 320: 277–280.

  • DeBerry C, Mou S and Linnekin D. . 1997 Biochem. J. 327: 73–80.

  • Disela C, Glineur C, Bugge T, Sap J, Stengl G, Dodgson J, Stunnenberg H, Beug H and Zenke M. . 1991 Genes Dev. 5: 2033–2047.

  • Dolznig H, Bartunek P, Nasmyth K, Müllner EW and Beug H. . 1995 Cell Growth Differ. 6: 1341–1352.

  • Gabbianelli M, Sargiacomo M, Pelosi E, Testa U, Isacchi G and Peschle C. . 1990 Science 249: 1561–1564.

  • Gabrilove JL, White K, Rahman Z and Wilson EL. . 1994 Blood 83: 907–910.

  • Garrido C, Li RP, Samarut J, Gospodarowicz D and Saule S. . 1993 Virology 192: 578–586.

  • Halevy O, Monsonego E, Marcelle C, Hodik V, Mett A and Pines M. . 1994 Exp. Cell Res. 212: 278–284.

  • Hanks SK, Quinn AM and Hunter T. . 1988 Science 241: 42–52.

  • Harrison ML, Isaacson CC, Burg DL, Geahlen RL and Low PS. . 1994 J. Biol. Chem. 269: 955–959.

  • Hayman MJ, Meyer S, Martin F, Steinlein P and Beug H. . 1993 Cell 74: 157–169.

  • Hoehn GT, Stokland T, Amin S, Ramirez M, Hawkins AL, Griffin CA, Small D and Civin CI. . 1996 Oncogene 12: 903–913.

  • Holzenberger M, Lapointe F, Leibovici M and Lievre CA. . 1996 Dev. Brain Res. 97: 76–87.

  • Hovens CM, Stacker SA, Andres AC, Harpur AG, Ziemiecki A and Wilks AF. . 1992 Proc. Natl. Acad. Sci. USA 89: 11818–11822.

  • Huber TL, Zhou Y, Mead PE and Zon LI. . 1998 Blood 92: 4128–4137.

  • Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K and Silvennoinen O. . 1995 Annu. Rev. Immunol. 13: 369–398.

  • Jia R and Hanafusa H. . 1994 J. Biol. Chem. 269: 1839–1844.

  • Johnson DE and Williams LT. . 1993 Adv. Cancer Res. 60: 1–41.

  • Kolanus W, Romeo C and Seed B. . 1993 Cell 74: 171–183.

  • Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar Sagi D, Lax I and Schlessinger J. . 1997 Cell 89: 693–702.

  • Kruh GD, Perego R, Miki T and Aaronson SA. . 1990 Proc. Natl. Acad. Sci. USA 87: 5802–5806.

  • Leutz A, Beug H and Graf T. . 1984 EMBO J. 3: 3191–3197.

  • Madruga J, Koritschoner N, Stengl G, Knespel S, Bartunek P and Zenke M. . 1997 Adv. Exp. Med. Biol. 417: 461–465.

  • Marcelle C and Eichmann A. . 1992 Oncogene 7: 2479–2487.

  • Marcelle C, Eichmann A, Halevy O, Breant C and Le Douarin NM. . 1994 Development 120: 683–694.

  • Marcelle C, Wolf J and Bronner-Fraser M. . 1995 Dev. Biol. 172: 100–114.

  • Mellitzer G, Wessely O, Decker T, Meinke A, Hayman MJ and Beug H. . 1996 Proc. Natl. Acad. Sci. USA 93: 9600–9605.

  • Muta K, Krantz SB, Bondurant MC and Wickrema A. . 1994 J. Clin. Invest. 94: 34–43.

  • Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G and Goldfarb M. . 1996 J. Biol. Chem. 271: 15292–15297.

  • Panzenböck B, Bartunek P, Mapara MY and Zenke M. . 1998 Blood 92: 3658–3668.

  • Partanen J, Makela TP, Alitalo R, Lehvaslaiho H and Alitalo K. . 1990 Proc. Natl. Acad. Sci. USA 87: 8913–8917.

  • Partanen J, Makela TP, Eerola E, Korhonen J, Hirvonen H, Claesson-Welsh L and Alitalo K. . 1991 EMBO J. 10: 1347–1354.

  • Pawson T and Scott JD. . 1997 Science 278: 2075–2080.

  • Radke K, Beug H, Kornfeld S and Graf T. . 1982 Cell 31: 643–653.

  • Robinson D, Chen H-C, Li D, Yustein JT, He F, Lin W-C, Hayman M and Kung H-S. . 1998 J. Biomed. Sci. 5: 93–100.

  • Sabe H, Knudsen B, Okada M, Nada S, Nakagawa H and Hanafusa H. . 1992 Proc. Natl. Acad. Sci. USA 89: 2190–2194.

  • Sasaki E, Okamura H, Chikamune T, Kanai Y, Watanabe M, Naito M and Sakurai M. . 1993 Gene 128: 257–261.

  • Sawada K, Krantz SB, Dessypris EN, Koury ST and Sawyer ST. . 1989 J. Clin. Invest. 83: 1701–1709.

  • Sawyers CL, Denny CT and Witte ON. . 1991 Cell 64: 337–350.

  • Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB and Parsons JT. . 1992 Proc. Natl. Acad. Sci. USA 89: 5192–5196.

  • Schlessinger J and Ullrich A. . 1992 Neuron 9: 383–391.

  • Schroeder C, Gibson L, Nordström C and Beug H. . 1993 EMBO J. 12: 951–960.

  • Simoneaux DK, Fletcher FA, Jurecic R, Shilling HG, Van NT, Patel P and Belmont JW. . 1995 J. Immunol. 154: 1157–1166.

  • Stark KL, McMahon JA and McMahon AP. . 1991 Development 113: 641–651.

  • Steinlein P, Wessely O, Meyer S, Deiner EM, Hayman MJ and Beug H. . 1995 Curr. Biol. 5: 191–204.

  • Tamagnone L, Partanen J, Armstrong E, Lasota J, Ohgami K, Tazunoki T, LaForgia S, Huebner K and Alitalo K. . 1993 Oncogene 8: 2009–2014.

  • Ullrich A and Schlessinger J. . 1990 Cell 61: 203–212.

  • Vainikka S, Joukov V, Klint P and Alitalo K. . 1996 J. Biol. Chem. 271: 1270–1273.

  • Vainikka S, Joukov V, Wennstrom S, Bergman M, Pelicci PG and Alitalo K. . 1994 J. Biol. Chem. 269: 18320–18326.

  • Vainikka S, Partanen J, Bellosta P, Coulier F, Birnbaum D, Basilico C, Jaye M and Alitalo K. . 1992 EMBO J. 11: 4273–4280.

  • Wang JK, Gao G and Goldfarb M. . 1994 Mol. Cell. Biol. 14: 181–188.

  • Wang JK and Goldfarb M. . 1997 Oncogene 14: 1767–1778.

  • Wessely O, Deiner E-M, Beug H and von Lindern M. . 1997 EMBO J. 16: 267–280.

  • Wilks AF. . 1991 Methods Enzymol. 200: 533–546.

  • Wilks AF, Kurban RR, Hovens CM and Ralph SJ. . 1989 Gene 85: 67–74.

  • Xu H, Lee KW and Goldfarb M. . 1998 J. Biol. Chem. 273: 17987–17990.

  • Yee K, Bishop TR, Mather C and Zon LI. . 1993 Blood 82: 1335–1343.

  • Yuen D, Mittal L, Deng C and Choi K. . 1998 Blood 91: 3202–3209.

  • Zenke M, Kahn P, Disela C, Vennström B, Leutz A, Keegan K, Hayman MJ, Choi HR, Yew N, Engel JD and Beug H. . 1988 Cell 52: 107–119.

Download references

Acknowledgements

We thank B Anzinger, S Diebold and J Madruga for helpful comments on this work and I Gallagher for typing the manuscript. NP Koritschoner was a recipient of a Max Delbrück post-doctoral fellowship.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koritschoner, N., Bartůněk, P., Knespel, S. et al. The fibroblast growth factor receptor FGFR-4 acts as a ligand dependent modulator of erythroid cell proliferation. Oncogene 18, 5904–5914 (1999). https://doi.org/10.1038/sj.onc.1202979

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202979

Keywords

This article is cited by

Search

Quick links