Home LiteratureArticle Details
PMID: 16597617 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family.

The Journal of biological chemistry ·Vol. 281 ·No. 23 ·2006-06-09 ·Pages 15694-700

Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM

Abstract

In mammals, fibroblast growth factors (FGFs) are encoded by 22 genes. FGFs bind and activate alternatively spliced forms of four tyrosine kinase FGF receptors (FGFRs 1-4). The spatial and temporal expression patterns of FGFs and FGFRs and the ability of specific ligand-receptor pairs to actively signal are important factors regulating FGF activity in a variety of biological processes. FGF signaling activity is regulated by the binding specificity of ligands and receptors and is modulated by extrinsic cofactors such as heparan sulfate proteoglycans. In previous studies, we have engineered BaF3 cell lines to express the seven principal FGFRs and used these cell lines to determine the receptor binding specificity of FGFs 1-9 by using relative mitogenic activity as the readout. Here we have extended these semiquantitative studies to assess the receptor binding specificity of the remaining FGFs 10-23. This study completes the mitogenesis-based comparison of receptor specificity of the entire FGF family under standard conditions and should help in interpreting and predicting in vivo biological activity.

MeSH Terms
Base Sequence Cell Line DNA Primers Fibroblast Growth Factors/metabolism Humans Receptors, Fibroblast Growth Factor/metabolism Recombinant Proteins/metabolism Reverse Transcriptase Polymerase Chain Reaction
Chemicals
DNA Primers Receptors, Fibroblast Growth Factor Recombinant Proteins Fibroblast Growth Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Zhang Xiuqin
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ibrahimi Omar A
Olsen Shaun K
Umemori Hisashi
Mohammadi Moosa
Ornitz David M
References (108)
108 references, click to expand
  1. Fgf8 signalling from the AER is essential for normal limb development.
    Nat Genet. 2000 Dec;26(4):460-3 PMID: 11101846
  2. Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14536-41 PMID: 11121055
  3. Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo.
    Mech Dev. 1998 Jun;74(1-2):175-7 PMID: 9651520
  4. Uncoupling fibroblast growth factor receptor 2 ligand binding specificity leads to Apert syndrome-like phenotypes.
    Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3641-3 PMID: 11274381
  5. Fibroblast growth factors.
    Genome Biol. 2001;2(3):REVIEWS3005 PMID: 11276432
  6. Male-to-female sex reversal in mice lacking fibroblast growth factor 9.
    Cell. 2001 Mar 23;104(6):875-89 PMID: 11290325
  7. FGF23, hypophosphatemia, and rickets: has phosphatonin been found?
    Proc Natl Acad Sci U S A. 2001 May 22;98(11):5945-6 PMID: 11371627
  8. Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling for cecal development in mouse.
    Dev Biol. 2004 Jan 1;265(1):61-74 PMID: 14697353
  9. Fgf10 is essential for limb and lung formation.
    Nat Genet. 1999 Jan;21(1):138-41 PMID: 9916808
  10. FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression.
    Development. 1999 Mar;126(6):1189-200 PMID: 10021338
  11. Signaling through fibroblast growth factor receptor 2b plays a key role in the development of the exocrine pancreas.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6267-72 PMID: 10339576
  12. Genomic structure, mapping, activity and expression of fibroblast growth factor 17.
    Mech Dev. 1999 May;83(1-2):165-78 PMID: 10381577
  13. Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene.
    Dev Dyn. 1999 Sep;216(1):72-88 PMID: 10474167
  14. Fgfr2 is required for limb outgrowth and lung-branching morphogenesis.
    Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11895-9 PMID: 10518547
  15. Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias.
    Eur J Hum Genet. 2005 Jan;13(1):118-20 PMID: 15470364
  16. How does Fgf signaling from the isthmic organizer induce midbrain and cerebellum development?
    Dev Growth Differ. 2004 Dec;46(6):487-94 PMID: 15610138
  17. Endocardial and epicardial derived FGF signals regulate myocardial proliferation and differentiation in vivo.
    Dev Cell. 2005 Jan;8(1):85-95 PMID: 15621532
  18. Understanding the molecular basis of Apert syndrome.
    Plast Reconstr Surg. 2005 Jan;115(1):264-70 PMID: 15622262
  19. An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia.
    Hum Mol Genet. 2005 Feb 1;14(3):385-90 PMID: 15590700
  20. Structural and sequence motifs in dermatan sulfate for promoting fibroblast growth factor-2 (FGF-2) and FGF-7 activity.
    J Biol Chem. 2005 Feb 18;280(7):5300-6 PMID: 15563459
  21. FGFR2b signaling regulates ex vivo submandibular gland epithelial cell proliferation and branching morphogenesis.
    Development. 2005 Mar;132(6):1223-34 PMID: 15716343
  22. Fibroblast growth factors 7 and 10 are expressed in the human embryonic pancreatic mesenchyme and promote the proliferation of embryonic pancreatic epithelial cells.
    Diabetologia. 2005 Feb;48(2):277-81 PMID: 15690149
  23. Fibroblast growth factor 23 reduces expression of type IIa Na+/Pi co-transporter by signaling through a receptor functionally distinct from the known FGFRs in opossum kidney cells.
    Genes Cells. 2005 May;10(5):489-502 PMID: 15836777
  24. Structural basis for fibroblast growth factor receptor activation.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):107-37 PMID: 15863029
  25. FGF signaling in flies and worms: more and more relevant to vertebrate biology.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):151-8 PMID: 15863031
  26. A naturally occurring secreted form of fibroblast growth factor (FGF) receptor 1 binds basic FGF in preference over acidic FGF.
    J Biol Chem. 1992 Aug 15;267(23):16076-80 PMID: 1379591
  27. Structural and functional diversity in the FGF receptor multigene family.
    Adv Cancer Res. 1993;60:1-41 PMID: 8417497
  28. Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy.
    Mol Cell Biol. 1993 Aug;13(8):4513-22 PMID: 7687739
  29. Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2).
    Dev Biol. 1993 Aug;158(2):475-86 PMID: 8393815
  30. Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA.
    Mol Cell Biol. 1993 Sep;13(9):5461-8 PMID: 8355693
  31. Keratinocyte growth factor functions in epithelial induction during seminal vesicle development.
    Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1074-8 PMID: 8302834
  32. Fibroblast growth factor receptor (FGFR) 3. Alternative splicing in immunoglobulin-like domain III creates a receptor highly specific for acidic FGF/FGF-1.
    J Biol Chem. 1994 Apr 15;269(15):11620-7 PMID: 7512569
  33. Hands and feet in the Apert syndrome.
    Am J Med Genet. 1995 May 22;57(1):82-96 PMID: 7645606
  34. Regulation of fibroblast growth factor-23 signaling by klotho.
    J Biol Chem. 2006 Mar 10;281(10):6120-3 PMID: 16436388
  35. FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains.
    Development. 2006 Apr;133(8):1507-17 PMID: 16540513
  36. FGF9 promotes survival of germ cells in the fetal testis.
    Development. 2006 Apr;133(8):1519-27 PMID: 16540514
  37. Expression of FGF23 is correlated with serum phosphate level in isolated fibrous dysplasia.
    Life Sci. 2006 Apr 11;78(20):2295-301 PMID: 16337659
  38. Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels.
    J Physiol. 2005 Nov 15;569(Pt 1):179-93 PMID: 16166153
  39. Subcellular and developmental expression of alternatively spliced forms of fibroblast growth factor 14.
    Mech Dev. 2000 Feb;90(2):283-7 PMID: 10640713
  40. FGFs, heparan sulfate and FGFRs: complex interactions essential for development.
    Bioessays. 2000 Feb;22(2):108-12 PMID: 10655030
  41. Specificities of heparan sulphate proteoglycans in developmental processes.
    Nature. 2000 Apr 13;404(6779):725-8 PMID: 10783877
  42. Fibroblast growth factor (FGF) receptor 1-IIIb is a naturally occurring functional receptor for FGFs that is preferentially expressed in the skin and the brain.
    J Biol Chem. 2000 May 26;275(21):16091-7 PMID: 10821861
  43. FGF signals for cell proliferation and migration through different pathways.
    Cytokine Growth Factor Rev. 2000 Dec;11(4):295-302 PMID: 10959077
  44. Fibroblast growth factors, their receptors and signaling.
    Endocr Relat Cancer. 2000 Sep;7(3):165-97 PMID: 11021964
  45. Fibroblast growth factor signaling in tumorigenesis.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):179-86 PMID: 15863033
  46. FGF signaling in the developing endochondral skeleton.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):205-13 PMID: 15863035
  47. Fibroblast growth factor homologous factors: evolution, structure, and function.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):215-20 PMID: 15863036
  48. FGF23 and disorders of phosphate homeostasis.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):221-32 PMID: 15863037
  49. Mechanisms underlying differential responses to FGF signaling.
    Cytokine Growth Factor Rev. 2005 Apr;16(2):233-47 PMID: 15863038
  50. FGF-21 as a novel metabolic regulator.
    J Clin Invest. 2005 Jun;115(6):1627-35 PMID: 15902306
  51. FGF receptor signaling at the crossroads of endocrine homeostasis and tumorigenesis.
    Horm Metab Res. 2005 Jun;37(6):355-60 PMID: 16001327
  52. An evolutionary history of the FGF superfamily.
    Bioessays. 2005 Aug;27(8):849-57 PMID: 16015590
  53. A protein canyon in the FGF-FGF receptor dimer selects from an à la carte menu of heparan sulfate motifs.
    Curr Opin Struct Biol. 2005 Oct;15(5):506-16 PMID: 16154740
  54. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis.
    Cell Metab. 2005 Oct;2(4):217-25 PMID: 16213224
  55. Analysis of the biochemical mechanisms for the endocrine actions of fibroblast growth factor-23.
    Endocrinology. 2005 Nov;146(11):4647-56 PMID: 16081635
  56. FGF17b and FGF18 have different midbrain regulatory properties from FGF8b or activated FGF receptors.
    Development. 2003 Dec;130(25):6175-85 PMID: 14602678
  57. Functions and regulations of fibroblast growth factor signaling during embryonic development.
    Dev Biol. 2005 Nov 15;287(2):390-402 PMID: 16216232
  58. Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development.
    Development. 2006 Jan;133(1):173-80 PMID: 16308329
  59. Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism.
    Eur J Endocrinol. 2006 Jan;154(1):93-9 PMID: 16381997
  60. Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndromes.
    Dev Cell. 2006 Jan;10(1):71-80 PMID: 16399079
  61. Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain.
    Genes Dev. 2006 Jan 15;20(2):185-98 PMID: 16384934
  62. Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity.
    Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):935-40 PMID: 14732692
  63. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis.
    J Bone Miner Res. 2004 Mar;19(3):429-35 PMID: 15040831
  64. Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis.
    Endocrinology. 2004 Jul;145(7):3087-94 PMID: 14988389
  65. Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate.
    J Clin Invest. 2004 Jun;113(12):1692-700 PMID: 15199404
  66. FGF22 and its close relatives are presynaptic organizing molecules in the mammalian brain.
    Cell. 2004 Jul 23;118(2):257-70 PMID: 15260994
  67. Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination.
    Development. 2004 Aug;131(15):3627-36 PMID: 15229180
  68. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons.
    J Neurosci. 2004 Jul 28;24(30):6765-75 PMID: 15282281
  69. Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair.
    Adv Cancer Res. 2004;91:69-136 PMID: 15327889
  70. Fgf9 signaling regulates inner ear morphogenesis through epithelial-mesenchymal interactions.
    Dev Biol. 2004 Sep 15;273(2):350-60 PMID: 15328018
  71. Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalities.
    Hum Mol Genet. 2004 Oct 1;13(19):2313-24 PMID: 15282208
  72. Evolution of the Fgf and Fgfr gene families.
    Trends Genet. 2004 Nov;20(11):563-9 PMID: 15475116
  73. Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor.
    Science. 1989 Jul 7;245(4913):57-60 PMID: 2544996
  74. The central nervous system in the Apert syndrome.
    Am J Med Genet. 1990 Jan;35(1):36-45 PMID: 2405668
  75. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
    Cell. 1991 Feb 22;64(4):841-8 PMID: 1847668
  76. Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation.
    Science. 1991 Jun 21;252(5013):1705-8 PMID: 1646484
  77. The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain.
    Mol Cell Biol. 1991 Sep;11(9):4627-34 PMID: 1652059
  78. Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells.
    Mol Cell Biol. 1992 Jan;12(1):240-7 PMID: 1309590
  79. Fibroblast growth factor homologous factor 1B binds to the C terminus of the tetrodotoxin-resistant sodium channel rNav1.9a (NaN).
    J Biol Chem. 2001 Jun 1;276(22):18925-33 PMID: 11376006
  80. Fibroblast growth factor homologous factors are intracellular signaling proteins.
    Curr Biol. 2001 May 15;11(10):793-7 PMID: 11378392
  81. Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7182-7 PMID: 11390973
  82. Lung hypoplasia and neonatal death in Fgf9-null mice identify this gene as an essential regulator of lung mesenchyme.
    Development. 2001 Jun;128(11):2095-106 PMID: 11493531
  83. Co-transcriptional splicing of pre-messenger RNAs: considerations for the mechanism of alternative splicing.
    Gene. 2001 Oct 17;277(1-2):31-47 PMID: 11602343
  84. Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition.
    J Cell Biol. 2001 Nov 26;155(5):845-58 PMID: 11724824
  85. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23.
    Kidney Int. 2001 Dec;60(6):2079-86 PMID: 11737582
  86. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18.
    Genes Dev. 2002 Apr 1;16(7):859-69 PMID: 11937493
  87. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease.
    Genes Dev. 2002 Jun 15;16(12):1446-65 PMID: 12080084
  88. Ataxia and paroxysmal dyskinesia in mice lacking axonally transported FGF14.
    Neuron. 2002 Jul 3;35(1):25-38 PMID: 12123606
  89. Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase.
    J Biol Chem. 2002 Dec 20;277(51):49111-9 PMID: 12244047
  90. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected].
    Am J Hum Genet. 2003 Jan;72(1):191-9 PMID: 12489043
  91. Modulation of the cardiac sodium channel Nav1.5 by fibroblast growth factor homologous factor 1B.
    J Biol Chem. 2003 Jan 10;278(2):1029-36 PMID: 12401812
  92. Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2266-71 PMID: 12591959
  93. Fibroblast growth factor (FGF) homologous factors share structural but not functional homology with FGFs.
    J Biol Chem. 2003 Sep 5;278(36):34226-36 PMID: 12815063
  94. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis.
    Genes Dev. 2002 Apr 1;16(7):870-9 PMID: 11937494
  95. FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting.
    J Clin Invest. 2003 Sep;112(5):683-92 PMID: 12952917
  96. Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly.
    J Cell Biol. 2003 Nov 10;163(3):637-48 PMID: 14610064
  97. Expression and biological activity of mouse fibroblast growth factor-9.
    J Biol Chem. 1996 Jan 19;271(3):1726-31 PMID: 8576175
  98. Receptor specificity of the fibroblast growth factor family.
    J Biol Chem. 1996 Jun 21;271(25):15292-7 PMID: 8663044
  99. Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9850-7 PMID: 8790420
  100. Of worms and men: an evolutionary perspective on the fibroblast growth factor (FGF) and FGF receptor families.
    J Mol Evol. 1997 Jan;44(1):43-56 PMID: 9010135
  101. Developmental expression of splicing variants of fibroblast growth factor receptor 3 (FGFR3) in mouse.
    Int J Dev Biol. 1996 Dec;40(6):1185-8 PMID: 9032024
  102. Chromosomal mapping of two novel human FGF genes, FGF11 and FGF12.
    Genomics. 1997 Feb 15;40(1):151-4 PMID: 9070933
  103. Murine FGF-12 and FGF-13: expression in embryonic nervous system, connective tissue and heart.
    Mech Dev. 1997 Jun;64(1-2):31-9 PMID: 9232594
  104. Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung.
    Development. 1997 Dec;124(23):4867-78 PMID: 9428423
  105. The heparan sulfate-fibroblast growth factor family: diversity of structure and function.
    Prog Nucleic Acid Res Mol Biol. 1998;59:135-76 PMID: 9427842
  106. Structure and expression of the mRNA encoding a novel fibroblast growth factor, FGF-18.
    J Biol Chem. 1998 Jul 17;273(29):18161-4 PMID: 9660775
  107. FGF-10 is a chemotactic factor for distal epithelial buds during lung development.
    Dev Biol. 1998 Sep 15;201(2):125-34 PMID: 9740653
  108. Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function.
    J Biol Chem. 1998 Oct 23;273(43):28116-21 PMID: 9774430
Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M601252200
Published
2006-06-09
Epub
2006-00-04
Pages
15694-700
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2080618
Subset
IM
Grants
NHLBI NIH HHS · HL076664 · United States
NIDCR NIH HHS · DE013686 · United States
NIDCR NIH HHS · R01 DE013686 · United States
NHLBI NIH HHS · R01 HL076664-03 · United States
NINDS NIH HHS · R01 NS065761 · United States
NHLBI NIH HHS · R01 HL076664 · United States
External Links
PubMed source DOI: 10.1074/jbc.M601252200 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2