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. 1991 Jun;10(6):1347–1354. doi: 10.1002/j.1460-2075.1991.tb07654.x

FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern.

J Partanen 1, T P Mäkelä 1, E Eerola 1, J Korhonen 1, H Hirvonen 1, L Claesson-Welsh 1, K Alitalo 1
PMCID: PMC452793  PMID: 1709094

Abstract

We have previously identified two novel members of the fibroblast growth factor receptor (FGFR) gene family expressed in K562 erythroleukemia cells. Here we report cDNA cloning and analysis of one of these genes, named FGFR-4. The deduced amino acid sequence of FGFR-4 is 55% identical with both previously characterized FGFRs, flg and bek, and has the structural characteristics of a FGFR family member including three immunoglobulin-like domains in its extracellular part. Antibodies raised against the carboxy terminus of FGFR-4 detected 95 and 110 kd glycoproteins with a protein backbone of 88 kd in COS cells transfected with a FGFR-4 cDNA expression vector. The FGFR-4 protein expressed in COS cells could also be affinity-labeled with radioiodinated acidic FGF. Furthermore, ligand binding experiments demonstrated that FGFR-4 binds acidic FGF with high affinity but does not bind basic FGF. FGFR-4 is expressed as a 3.0 kb mRNA in the adrenal, lung, kidney, liver, pancreas, intestine, striated muscle and spleen tissues of human fetuses. The expression pattern of FGFR-4 is distinct from that of flg and bek and the yet additional member of the same gene family, FGFR-3, which we have also cloned from the K562 leukemia cells. Our results suggest that FGFR-4 along with other fibroblast growth factor receptors performs cell lineage and tissue-specific functions.

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Selected References

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

  1. Abraham J. A., Whang J. L., Tumolo A., Mergia A., Friedman J., Gospodarowicz D., Fiddes J. C. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J. 1986 Oct;5(10):2523–2528. doi: 10.1002/j.1460-2075.1986.tb04530.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bottaro D. P., Rubin J. S., Ron D., Finch P. W., Florio C., Aaronson S. A. Characterization of the receptor for keratinocyte growth factor. Evidence for multiple fibroblast growth factor receptors. J Biol Chem. 1990 Aug 5;265(22):12767–12770. [PubMed] [Google Scholar]
  3. Burgess W. H., Maciag T. The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58:575–606. doi: 10.1146/annurev.bi.58.070189.003043. [DOI] [PubMed] [Google Scholar]
  4. Claude P., Parada I. M., Gordon K. A., D'Amore P. A., Wagner J. A. Acidic fibroblast growth factor stimulates adrenal chromaffin cells to proliferate and to extend neurites, but is not a long-term survival factor. Neuron. 1988 Nov;1(9):783–790. doi: 10.1016/0896-6273(88)90126-2. [DOI] [PubMed] [Google Scholar]
  5. Delli Bovi P., Curatola A. M., Kern F. G., Greco A., Ittmann M., Basilico C. An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family. Cell. 1987 Aug 28;50(5):729–737. doi: 10.1016/0092-8674(87)90331-x. [DOI] [PubMed] [Google Scholar]
  6. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dionne C. A., Crumley G., Bellot F., Kaplow J. M., Searfoss G., Ruta M., Burgess W. H., Jaye M., Schlessinger J. Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J. 1990 Sep;9(9):2685–2692. doi: 10.1002/j.1460-2075.1990.tb07454.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Finch P. W., Rubin J. S., Miki T., Ron D., Aaronson S. A. Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science. 1989 Aug 18;245(4919):752–755. doi: 10.1126/science.2475908. [DOI] [PubMed] [Google Scholar]
  9. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  10. Gabbianelli M., Sargiacomo M., Pelosi E., Testa U., Isacchi G., Peschle C. "Pure" human hematopoietic progenitors: permissive action of basic fibroblast growth factor. Science. 1990 Sep 28;249(4976):1561–1564. doi: 10.1126/science.2218497. [DOI] [PubMed] [Google Scholar]
  11. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  12. Hattori Y., Odagiri H., Nakatani H., Miyagawa K., Naito K., Sakamoto H., Katoh O., Yoshida T., Sugimura T., Terada M. K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5983–5987. doi: 10.1073/pnas.87.15.5983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hou J. Z., Kan M. K., McKeehan K., McBride G., Adams P., McKeehan W. L. Fibroblast growth factor receptors from liver vary in three structural domains. Science. 1991 Feb 8;251(4994):665–668. doi: 10.1126/science.1846977. [DOI] [PubMed] [Google Scholar]
  14. Houssaint E., Blanquet P. R., Champion-Arnaud P., Gesnel M. C., Torriglia A., Courtois Y., Breathnach R. Related fibroblast growth factor receptor genes exist in the human genome. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8180–8184. doi: 10.1073/pnas.87.20.8180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jaye M., Howk R., Burgess W., Ricca G. A., Chiu I. M., Ravera M. W., O'Brien S. J., Modi W. S., Maciag T., Drohan W. N. Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization. Science. 1986 Aug 1;233(4763):541–545. doi: 10.1126/science.3523756. [DOI] [PubMed] [Google Scholar]
  16. Johnson D. E., Lee P. L., Lu J., Williams L. T. Diverse forms of a receptor for acidic and basic fibroblast growth factors. Mol Cell Biol. 1990 Sep;10(9):4728–4736. doi: 10.1128/mcb.10.9.4728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kazlauskas A., Cooper J. A. Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Cell. 1989 Sep 22;58(6):1121–1133. doi: 10.1016/0092-8674(89)90510-2. [DOI] [PubMed] [Google Scholar]
  18. Keegan K., Johnson D. E., Williams L. T., Hayman M. J. Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1095–1099. doi: 10.1073/pnas.88.4.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kimelman D., Abraham J. A., Haaparanta T., Palisi T. M., Kirschner M. W. The presence of fibroblast growth factor in the frog egg: its role as a natural mesoderm inducer. Science. 1988 Nov 18;242(4881):1053–1056. doi: 10.1126/science.3194757. [DOI] [PubMed] [Google Scholar]
  20. Kornbluth S., Paulson K. E., Hanafusa H. Novel tyrosine kinase identified by phosphotyrosine antibody screening of cDNA libraries. Mol Cell Biol. 1988 Dec;8(12):5541–5544. doi: 10.1128/mcb.8.12.5541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lee P. L., Johnson D. E., Cousens L. S., Fried V. A., Williams L. T. Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor. Science. 1989 Jul 7;245(4913):57–60. doi: 10.1126/science.2544996. [DOI] [PubMed] [Google Scholar]
  23. Lehväslaiho H., Lehtola L., Sistonen L., Alitalo K. A chimeric EGF-R-neu proto-oncogene allows EGF to regulate neu tyrosine kinase and cell transformation. EMBO J. 1989 Jan;8(1):159–166. doi: 10.1002/j.1460-2075.1989.tb03360.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mansukhani A., Moscatelli D., Talarico D., Levytska V., Basilico C. A murine fibroblast growth factor (FGF) receptor expressed in CHO cells is activated by basic FGF and Kaposi FGF. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4378–4382. doi: 10.1073/pnas.87.11.4378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Marics I., Adelaide J., Raybaud F., Mattei M. G., Coulier F., Planche J., de Lapeyriere O., Birnbaum D. Characterization of the HST-related FGF.6 gene, a new member of the fibroblast growth factor gene family. Oncogene. 1989 Mar;4(3):335–340. [PubMed] [Google Scholar]
  26. McCutchan J. H., Pagano J. S. Enchancement of the infectivity of simian virus 40 deoxyribonucleic acid with diethylaminoethyl-dextran. J Natl Cancer Inst. 1968 Aug;41(2):351–357. [PubMed] [Google Scholar]
  27. Miki T., Fleming T. P., Bottaro D. P., Rubin J. S., Ron D., Aaronson S. A. Expression cDNA cloning of the KGF receptor by creation of a transforming autocrine loop. Science. 1991 Jan 4;251(4989):72–75. doi: 10.1126/science.1846048. [DOI] [PubMed] [Google Scholar]
  28. Moscatelli D. High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells. J Cell Physiol. 1987 Apr;131(1):123–130. doi: 10.1002/jcp.1041310118. [DOI] [PubMed] [Google Scholar]
  29. Partanen J., Mäkelä T. P., Alitalo R., Lehväslaiho H., Alitalo K. Putative tyrosine kinases expressed in K-562 human leukemia cells. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8913–8917. doi: 10.1073/pnas.87.22.8913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pasquale E. B. A distinctive family of embryonic protein-tyrosine kinase receptors. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5812–5816. doi: 10.1073/pnas.87.15.5812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pasquale E. B., Singer S. J. Identification of a developmentally regulated protein-tyrosine kinase by using anti-phosphotyrosine antibodies to screen a cDNA expression library. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5449–5453. doi: 10.1073/pnas.86.14.5449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Poncz M., Surrey S., LaRocco P., Weiss M. J., Rappaport E. F., Conway T. M., Schwartz E. Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line. Blood. 1987 Jan;69(1):219–223. [PubMed] [Google Scholar]
  33. Reid H. H., Wilks A. F., Bernard O. Two forms of the basic fibroblast growth factor receptor-like mRNA are expressed in the developing mouse brain. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1596–1600. doi: 10.1073/pnas.87.4.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ruta M., Burgess W., Givol D., Epstein J., Neiger N., Kaplow J., Crumley G., Dionne C., Jaye M., Schlessinger J. Receptor for acidic fibroblast growth factor is related to the tyrosine kinase encoded by the fms-like gene (FLG). Proc Natl Acad Sci U S A. 1989 Nov;86(22):8722–8726. doi: 10.1073/pnas.86.22.8722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Safran A., Avivi A., Orr-Urtereger A., Neufeld G., Lonai P., Givol D., Yarden Y. The murine flg gene encodes a receptor for fibroblast growth factor. Oncogene. 1990 May;5(5):635–643. [PubMed] [Google Scholar]
  36. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Slack J. M., Darlington B. G., Heath J. K., Godsave S. F. Mesoderm induction in early Xenopus embryos by heparin-binding growth factors. Nature. 1987 Mar 12;326(6109):197–200. doi: 10.1038/326197a0. [DOI] [PubMed] [Google Scholar]
  38. Smith R., Peters G., Dickson C. Multiple RNAs expressed from the int-2 gene in mouse embryonal carcinoma cell lines encode a protein with homology to fibroblast growth factors. EMBO J. 1988 Apr;7(4):1013–1022. doi: 10.1002/j.1460-2075.1988.tb02908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stacey A., Schnieke A. SVpoly: a versatile mammalian expression vector. Nucleic Acids Res. 1990 May 11;18(9):2829–2829. doi: 10.1093/nar/18.9.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stanley K. K., Luzio J. P. Construction of a new family of high efficiency bacterial expression vectors: identification of cDNA clones coding for human liver proteins. EMBO J. 1984 Jun;3(6):1429–1434. doi: 10.1002/j.1460-2075.1984.tb01988.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Stemple D. L., Mahanthappa N. K., Anderson D. J. Basic FGF induces neuronal differentiation, cell division, and NGF dependence in chromaffin cells: a sequence of events in sympathetic development. Neuron. 1988 Aug;1(6):517–525. doi: 10.1016/0896-6273(88)90182-1. [DOI] [PubMed] [Google Scholar]
  42. Thomas K. A., Rios-Candelore M., Giménez-Gallego G., DiSalvo J., Bennett C., Rodkey J., Fitzpatrick S. Pure brain-derived acidic fibroblast growth factor is a potent angiogenic vascular endothelial cell mitogen with sequence homology to interleukin 1. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6409–6413. doi: 10.1073/pnas.82.19.6409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Thompson J. A., Haudenschild C. C., Anderson K. D., DiPietro J. M., Anderson W. F., Maciag T. Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7928–7932. doi: 10.1073/pnas.86.20.7928. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  44. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  45. Wanaka A., Johnson E. M., Jr, Milbrandt J. Localization of FGF receptor mRNA in the adult rat central nervous system by in situ hybridization. Neuron. 1990 Sep;5(3):267–281. doi: 10.1016/0896-6273(90)90164-b. [DOI] [PubMed] [Google Scholar]
  46. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  47. Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P. F., Terada M., Sugimura T. Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7305–7309. doi: 10.1073/pnas.84.20.7305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Zhan X., Bates B., Hu X. G., Goldfarb M. The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors. Mol Cell Biol. 1988 Aug;8(8):3487–3495. doi: 10.1128/mcb.8.8.3487. [DOI] [PMC free article] [PubMed] [Google Scholar]

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