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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Fibroblast growth factor 4''' is a [[protein]] that in humans is encoded by the ''FGF4'' [[gene]].<ref name="pmid1611909">{{cite journal | vauthors = Galland F, Stefanova M, Lafage M, Birnbaum D | title = Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23 | journal = Cytogenetics and Cell Genetics | volume = 60 | issue = 2 | pages = 114–6 | date = Jul 1992 | pmid = 1611909 | pmc = | doi = 10.1159/000133316 }}</ref><ref name="entrez"/>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The protein encoded by this gene is a member of the [[fibroblast growth factor]] (FGF) family. FGF family members possess broad [[mitogenic]] and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, [[morphogenesis]], tissue repair, tumor growth and invasion. This gene was identified by its oncogenic transforming activity. This gene and [[FGF3]], another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog ([[Sonic hedgehog|SHH]]) signaling pathway.<ref name="entrez">{{cite web | title = Entrez Gene: FGF4 fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2249| accessdate = }}</ref>
{{GNF_Protein_box
| image = PBB_Protein_FGF4_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ijt.
| PDB = {{PDB2|1ijt}}
| Name = Fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene)
| HGNCid = 3682
| Symbol = FGF4
| AltSymbols =; HBGF-4; HST; HST-1; HSTF1; K-FGF; KFGF
| OMIM = 164980
| ECnumber = 
| Homologene = 1522
| MGIid = 95518
| GeneAtlas_image1 = PBB_GE_FGF4_206783_at_tn.png
| Function = {{GNF_GO|id=GO:0008083 |text = growth factor activity}} {{GNF_GO|id=GO:0008201 |text = heparin binding}}
| Component = {{GNF_GO|id=GO:0005575 |text = cellular_component}} {{GNF_GO|id=GO:0005576 |text = extracellular region}}
| Process = {{GNF_GO|id=GO:0000074 |text = regulation of progression through cell cycle}} {{GNF_GO|id=GO:0007067 |text = mitosis}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0019827 |text = stem cell maintenance}} {{GNF_GO|id=GO:0035116 |text = embryonic hindlimb morphogenesis}} {{GNF_GO|id=GO:0042475 |text = odontogenesis (sensu Vertebrata)}} {{GNF_GO|id=GO:0043066 |text = negative regulation of apoptosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2249
    | Hs_Ensembl = ENSG00000075388
    | Hs_RefseqProtein = NP_001998
    | Hs_RefseqmRNA = NM_002007
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 11
    | Hs_GenLoc_start = 69296978
    | Hs_GenLoc_end = 69299352
    | Hs_Uniprot = P08620
    | Mm_EntrezGene = 14175
    | Mm_Ensembl = ENSMUSG00000050917
    | Mm_RefseqmRNA = NM_010202
    | Mm_RefseqProtein = NP_034332
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 144670776
    | Mm_GenLoc_end = 144674633
    | Mm_Uniprot = Q542N0
  }}
}}
'''Fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene)''', also known as '''FGF4''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: FGF4 fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2249| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
| section_title =  
| summary_text = The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway.<ref name="entrez">{{cite web | title = Entrez Gene: FGF4 fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2249| accessdate = }}</ref>
}}


==References==
During embryonic development, the 21-kD protein FGF4 functions as a signaling molecule that is involved in many important processes.<ref name="Feldman_1995">{{cite journal | vauthors = Feldman B, Poueymirou W, Papaioannou VE, DeChiara TM, Goldfarb M | title = Requirement of FGF-4 for postimplantation mouse development | journal = Science | volume = 267 | issue = 5195 | pages = 246–9 | date = Jan 1995 | pmid = 7809630 | doi = 10.1126/science.7809630 }}</ref><ref name="pmid7590241">{{cite journal | vauthors = Yuan H, Corbi N, Basilico C, Dailey L | title = Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3 | journal = Genes & Development | volume = 9 | issue = 21 | pages = 2635–45 | date = Nov 1995 | pmid = 7590241 | doi = 10.1101/gad.9.21.2635 }}</ref> Studies using Fgf4 gene knockout mice showed developmental defects in embryos both in vivo and in vitro, revealing that FGF4 facilitates the survival and growth of the inner cell mass during the postimplantation phase of development by acting as an autocrine or paracrine ligand.<ref name="Feldman_1995"/> FGFs produced in the apical ectodermal ridge (AER) are critical for the proper forelimb and hindlimb outgrowth.<ref name="Boulet_2004">{{cite journal | vauthors = Boulet AM, Moon AM, Arenkiel BR, Capecchi MR | title = The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth | journal = Developmental Biology | volume = 273 | issue = 2 | pages = 361–72 | date = Sep 2004 | pmid = 15328019 | doi = 10.1016/j.ydbio.2004.06.012 }}</ref> FGF signaling in the AER is involved in regulating limb digit number and cell death in the interdigital mesenchyme.<ref name="Lu_2006">{{cite journal | vauthors = Lu P, Minowada G, Martin GR | title = Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function | journal = Development | volume = 133 | issue = 1 | pages = 33–42 | date = Jan 2006 | pmid = 16308330 | doi = 10.1242/dev.02172 }}</ref> When FGF signaling dynamics and regulatory processes are altered, postaxial polydactyly and cutaneous syndactyly, two phenotypic abnormalities collectively known as [[syndactyly|polysyndactyly]], can occur in the limbs. Polysyndactyly is observed when an excess of Fgf4 is expressed in limb buds of wild-type mice. In mutant limb buds that do not express [[FGF8|Fgf8]], the expression of Fgf4 still results in polysyndactyly, but Fgf4 is also able to rescue all skeletal defects that arise from the lack of Fgf8. Therefore, the Fgf4 gene compensates for the loss of the Fgf8 gene, revealing that FGF4 and FGF8 perform similar functions in limb skeleton patterning and limb development.<ref name="Lu_2006"/> Studies of zebrafish Fgf4 knockdown embryos demonstrated that when Fgf4 signaling is inhibited, randomized left-right patterning of the liver, pancreas, and heart takes place, showing that Fgf4 is a crucial gene involved in developing left-right patterning of visceral organs. Furthermore, unlike the role of FGF4 in limb development, FGF4 and FGF8 have distinct roles and function independently in the process of visceral organ left-right patterning.<ref name="Yamauchi_2009">{{cite journal | vauthors = Yamauchi H, Miyakawa N, Miyake A, Itoh N | title = Fgf4 is required for left-right patterning of visceral organs in zebrafish | journal = Developmental Biology | volume = 332 | issue = 1 | pages = 177–85 | date = Aug 2009 | pmid = 19481538 | doi = 10.1016/j.ydbio.2009.05.568 }}</ref>
{{reflist|2}}
Fgf signaling pathway has also been demonstrated to drive hindgut identity during gastrointestinal development, and the up regulation of the Fgf4 in pluripotent stem cell has been used to direct their differentiation for the generation of intestinal [[Organoids]] and tissues in vitro.<ref name="pmid25035496">{{cite journal | vauthors = Lancaster MA, Knoblich JA | title = Organogenesis in a dish: modeling development and disease using organoid technologies | journal = Science  | volume = 345 | issue = 6194 | pages = 1247125 | year = 2014 | pmid = 25035496 | doi = 10.1126/science.1247125 }}</ref>
==Further reading==
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Powers CJ, McLeskey SW, Wellstein A | title = Fibroblast growth factors, their receptors and signaling | journal = Endocrine-Related Cancer | volume = 7 | issue = 3 | pages = 165–97 | date = Sep 2000 | pmid = 11021964 | doi = 10.1677/erc.0.0070165 }}
| citations =
* {{cite journal | vauthors = Taira M, Yoshida T, Miyagawa K, Sakamoto H, Terada M, Sugimura T | title = cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 9 | pages = 2980–4 | date = May 1987 | pmid = 2953031 | pmc = 304784 | doi = 10.1073/pnas.84.9.2980 }}
*{{cite journal | author=Powers CJ, McLeskey SW, Wellstein A |title=Fibroblast growth factors, their receptors and signaling. |journal=Endocr. Relat. Cancer |volume=7 |issue= 3 |pages= 165-97 |year= 2000 |pmid= 11021964 |doi= }}
* {{cite journal | vauthors = Delli Bovi P, Curatola AM, Kern FG, Greco A, Ittmann M, Basilico C | title = An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family | journal = Cell | volume = 50 | issue = 5 | pages = 729–37 | date = Aug 1987 | pmid = 2957062 | doi = 10.1016/0092-8674(87)90331-X }}
*{{cite journal | author=Galland F, Stefanova M, Lafage M, Birnbaum D |title=Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23. |journal=Cytogenet. Cell Genet. |volume=60 |issue= 2 |pages= 114-6 |year= 1992 |pmid= 1611909 |doi= }}
* {{cite journal | vauthors = Yoshida T, Miyagawa K, Odagiri H, Sakamoto H, Little PF, Terada M, Sugimura T | title = Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 20 | pages = 7305–9 | date = Oct 1987 | pmid = 2959959 | pmc = 299281 | doi = 10.1073/pnas.84.20.7305 }}
*{{cite journal | author=Taira M, Yoshida T, Miyagawa K, ''et al.'' |title=cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 9 |pages= 2980-4 |year= 1987 |pmid= 2953031 |doi= }}
* {{cite journal | vauthors = Wada A, Sakamoto H, Katoh O, Yoshida T, Yokota J, Little PF, Sugimura T, Terada M | title = Two homologous oncogenes, HST1 and INT2, are closely located in human genome | journal = Biochemical and Biophysical Research Communications | volume = 157 | issue = 2 | pages = 828–35 | date = Dec 1988 | pmid = 2974287 | doi = 10.1016/S0006-291X(88)80324-3 }}
*{{cite journal | author=Delli Bovi P, Curatola AM, Kern FG, ''et al.'' |title=An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family. |journal=Cell |volume=50 |issue= 5 |pages= 729-37 |year= 1987 |pmid= 2957062 |doi= }}
* {{cite journal | vauthors = Huebner K, Ferrari AC, Delli Bovi P, Croce CM, Basilico C | title = The FGF-related oncogene, K-FGF, maps to human chromosome region 11q13, possibly near int-2 | journal = Oncogene Research | volume = 3 | issue = 3 | pages = 263–70 | year = 1989 | pmid = 3060803 | doi =  }}
*{{cite journal | author=Yoshida T, Miyagawa K, Odagiri H, ''et al.'' |title=Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 20 |pages= 7305-9 |year= 1987 |pmid= 2959959 |doi= }}
* {{cite journal | vauthors = Adelaide J, Mattei MG, Marics I, Raybaud F, Planche J, De Lapeyriere O, Birnbaum D | title = Chromosomal localization of the hst oncogene and its co-amplification with the int.2 oncogene in a human melanoma | journal = Oncogene | volume = 2 | issue = 4 | pages = 413–6 | date = Apr 1988 | pmid = 3283658 | doi =  }}
*{{cite journal | author=Wada A, Sakamoto H, Katoh O, ''et al.'' |title=Two homologous oncogenes, HST1 and INT2, are closely located in human genome. |journal=Biochem. Biophys. Res. Commun. |volume=157 |issue= 2 |pages= 828-35 |year= 1989 |pmid= 2974287 |doi=  }}
* {{cite journal | vauthors = Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M | title = Receptor specificity of the fibroblast growth factor family | journal = The Journal of Biological Chemistry | volume = 271 | issue = 25 | pages = 15292–7 | date = Jun 1996 | pmid = 8663044 | doi = 10.1074/jbc.271.25.15292 }}
*{{cite journal | author=Huebner K, Ferrari AC, Delli Bovi P, ''et al.'' |title=The FGF-related oncogene, K-FGF, maps to human chromosome region 11q13, possibly near int-2. |journal=Oncogene Res. |volume=3 |issue= 3 |pages= 263-70 |year= 1989 |pmid= 3060803 |doi=  }}
* {{cite journal  | author=Tanaka S |title=Promotion of trophoblast stem cell proliferation by FGF-4|journal=Science |volume=282 |pages= 2072–2075 |year= 1998 |doi= 10.1126/science.282.5396.2072 |display-authors=etal}}
*{{cite journal | author=Adelaide J, Mattei MG, Marics I, ''et al.'' |title=Chromosomal localization of the hst oncogene and its co-amplification with the int.2 oncogene in a human melanoma. |journal=Oncogene |volume=2 |issue= 4 |pages= 413-6 |year= 1988 |pmid= 3283658 |doi= }}
* {{cite journal | vauthors = Helland R, Berglund GI, Otlewski J, Apostoluk W, Andersen OA, Willassen NP, Smalås AO | title = High-resolution structures of three new trypsin-squash-inhibitor complexes: a detailed comparison with other trypsins and their complexes | journal = Acta Crystallographica Section D | volume = 55 | issue = Pt 1 | pages = 139–48 | date = Jan 1999 | pmid = 10089404 | doi = 10.1107/S090744499801052X }}
*{{cite journal  | author=Ornitz DM, Xu J, Colvin JS, ''et al.'' |title=Receptor specificity of the fibroblast growth factor family. |journal=J. Biol. Chem. |volume=271 |issue= 25 |pages= 15292-7 |year= 1996 |pmid= 8663044 |doi= }}
* {{cite journal | vauthors = Bellosta P, Iwahori A, Plotnikov AN, Eliseenkova AV, Basilico C, Mohammadi M | title = Identification of receptor and heparin binding sites in fibroblast growth factor 4 by structure-based mutagenesis | journal = Molecular and Cellular Biology | volume = 21 | issue = 17 | pages = 5946–57 | date = Sep 2001 | pmid = 11486033 | pmc = 87313 | doi = 10.1128/MCB.21.17.5946-5957.2001 }}
*{{cite journal | author=Helland R, Berglund GI, Otlewski J, ''et al.'' |title=High-resolution structures of three new trypsin-squash-inhibitor complexes: a detailed comparison with other trypsins and their complexes. |journal=Acta Crystallogr. D Biol. Crystallogr. |volume=55 |issue= Pt 1 |pages= 139-48 |year= 1999 |pmid= 10089404 |doi= 10.1107/S090744499801052X }}
* {{cite journal | vauthors = Britto JA, Evans RD, Hayward RD, Jones BM | title = From genotype to phenotype: the differential expression of FGF, FGFR, and TGFbeta genes characterizes human cranioskeletal development and reflects clinical presentation in FGFR syndromes | journal = Plastic and Reconstructive Surgery | volume = 108 | issue = 7 | pages = 2026–39; discussion 2040–6 | date = Dec 2001 | pmid = 11743396 | doi = 10.1097/00006534-200112000-00030 }}
*{{cite journal | author=Bellosta P, Iwahori A, Plotnikov AN, ''et al.'' |title=Identification of receptor and heparin binding sites in fibroblast growth factor 4 by structure-based mutagenesis. |journal=Mol. Cell. Biol. |volume=21 |issue= 17 |pages= 5946-57 |year= 2001 |pmid= 11486033 |doi= }}
* {{cite journal | vauthors = Yamamoto H, Ochiya T, Tamamushi S, Toriyama-Baba H, Takahama Y, Hirai K, Sasaki H, Sakamoto H, Saito I, Iwamoto T, Kakizoe T, Terada M | title = HST-1/FGF-4 gene activation induces spermatogenesis and prevents adriamycin-induced testicular toxicity | journal = Oncogene | volume = 21 | issue = 6 | pages = 899–908 | date = Jan 2002 | pmid = 11840335 | doi = 10.1038/sj.onc.1205135 }}
*{{cite journal | author=Britto JA, Evans RD, Hayward RD, Jones BM |title=From genotype to phenotype: the differential expression of FGF, FGFR, and TGFbeta genes characterizes human cranioskeletal development and reflects clinical presentation in FGFR syndromes. |journal=Plast. Reconstr. Surg. |volume=108 |issue= 7 |pages= 2026-39; discussion 2040-6 |year= 2002 |pmid= 11743396 |doi= }}
* {{cite journal | vauthors = Sieuwerts AM, Martens JW, Dorssers LC, Klijn JG, Foekens JA | title = Differential effects of fibroblast growth factors on expression of genes of the plasminogen activator and insulin-like growth factor systems by human breast fibroblasts | journal = Thrombosis and Haemostasis | volume = 87 | issue = 4 | pages = 674–83 | date = Apr 2002 | pmid = 12008951 | doi =  }}
*{{cite journal | author=Yamamoto H, Ochiya T, Tamamushi S, ''et al.'' |title=HST-1/FGF-4 gene activation induces spermatogenesis and prevents adriamycin-induced testicular toxicity. |journal=Oncogene |volume=21 |issue= 6 |pages= 899-908 |year= 2002 |pmid= 11840335 |doi= 10.1038/sj.onc.1205135 }}
* {{cite journal | vauthors = Koh KR, Ohta K, Nakamae H, Hino M, Yamane T, Takubo T, Tatsumi N | title = Differential effects of fibroblast growth factor-4, epidermal growth factor and transforming growth factor-beta1 on functional development of stromal layers in acute myeloid leukemia | journal = Leukemia Research | volume = 26 | issue = 10 | pages = 933–8 | date = Oct 2002 | pmid = 12163055 | doi = 10.1016/S0145-2126(02)00033-4 }}
*{{cite journal | author=Sieuwerts AM, Martens JW, Dorssers LC, ''et al.'' |title=Differential effects of fibroblast growth factors on expression of genes of the plasminogen activator and insulin-like growth factor systems by human breast fibroblasts. |journal=Thromb. Haemost. |volume=87 |issue= 4 |pages= 674-83 |year= 2003 |pmid= 12008951 |doi=  }}
* {{cite journal | vauthors = Lopez-Sanchez C, Climent V, Schoenwolf GC, Alvarez IS, Garcia-Martinez V | title = Induction of cardiogenesis by Hensen's node and fibroblast growth factors | journal = Cell and Tissue Research | volume = 309 | issue = 2 | pages = 237–49 | date = Aug 2002 | pmid = 12172783 | doi = 10.1007/s00441-002-0567-2 }}
*{{cite journal | author=Koh KR, Ohta K, Nakamae H, ''et al.'' |title=Differential effects of fibroblast growth factor-4, epidermal growth factor and transforming growth factor-beta1 on functional development of stromal layers in acute myeloid leukemia. |journal=Leuk. Res. |volume=26 |issue= 10 |pages= 933-8 |year= 2002 |pmid= 12163055 |doi= }}
* {{cite journal | vauthors = Wang P, Branch DR, Bali M, Schultz GA, Goss PE, Jin T | title = The POU homeodomain protein OCT3 as a potential transcriptional activator for fibroblast growth factor-4 (FGF-4) in human breast cancer cells | journal = The Biochemical Journal | volume = 375 | issue = Pt 1 | pages = 199–205 | date = Oct 2003 | pmid = 12841847 | pmc = 1223663 | doi = 10.1042/BJ20030579 }}
*{{cite journal | author=Lopez-Sanchez C, Climent V, Schoenwolf GC, ''et al.'' |title=Induction of cardiogenesis by Hensen's node and fibroblast growth factors. |journal=Cell Tissue Res. |volume=309 |issue= 2 |pages= 237-49 |year= 2003 |pmid= 12172783 |doi= 10.1007/s00441-002-0567-2 }}
* {{cite journal | vauthors = Reményi A, Lins K, Nissen LJ, Reinbold R, Schöler HR, Wilmanns M | title = Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers | journal = Genes & Development | volume = 17 | issue = 16 | pages = 2048–59 | date = Aug 2003 | pmid = 12923055 | pmc = 196258 | doi = 10.1101/gad.269303 }}
*{{cite journal | author=Wang P, Branch DR, Bali M, ''et al.'' |title=The POU homeodomain protein OCT3 as a potential transcriptional activator for fibroblast growth factor-4 (FGF-4) in human breast cancer cells. |journal=Biochem. J. |volume=375 |issue= Pt 1 |pages= 199-205 |year= 2003 |pmid= 12841847 |doi= 10.1042/BJ20030579 }}
* {{cite journal | vauthors = Hirai K, Sasaki H, Yamamoto H, Sakamoto H, Kubota Y, Kakizoe T, Terada M, Ochiya T | title = HST-1/FGF-4 protects male germ cells from apoptosis under heat-stress condition | journal = Experimental Cell Research | volume = 294 | issue = 1 | pages = 77–85 | date = Mar 2004 | pmid = 14980503 | doi = 10.1016/j.yexcr.2003.11.012 }}
*{{cite journal | author=Reményi A, Lins K, Nissen LJ, ''et al.'' |title=Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. |journal=Genes Dev. |volume=17 |issue= 16 |pages= 2048-59 |year= 2003 |pmid= 12923055 |doi= 10.1101/gad.269303 }}
* {{cite journal | vauthors = Grigor'eva EV, Shevchenko AI, Mazurok NA, Elisaphenko EA, Zhelezova AI, Shilov AG, Dyban PA, Dyban AP, Noniashvili EM, Slobodyanyuk SY, Nesterova TB, Brockdorff N, Zakian SM | title = FGF4 independent derivation of trophoblast stem cells from the common vole | journal = PLOS ONE | volume = 4 | issue = 9 | pages = e7161 | year = 2009 | pmid = 19777059 | doi = 10.1371/journal.pone.0007161 | pmc=2744875}}
*{{cite journal | author=Hirai K, Sasaki H, Yamamoto H, ''et al.'' |title=HST-1/FGF-4 protects male germ cells from apoptosis under heat-stress condition. |journal=Exp. Cell Res. |volume=294 |issue= 1 |pages= 77-85 |year= 2004 |pmid= 14980503 |doi= 10.1016/j.yexcr.2003.11.012 }}
* {{cite journal | vauthors = Boulet AM, Capecchi MR | title = Signaling by FGF4 and FGF8 is required for axial elongation of the mouse embryo | journal = Developmental Biology | volume = 371 | issue = 2 | pages = 235–45 | date = Nov 2012 | pmid = 22954964 | doi = 10.1016/j.ydbio.2012.08.017 | pmc=3481862}}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{PDB Gallery|geneid=2249}}
{{Growth factors}}
{{Intercellular signaling peptides and proteins}}
{{Intercellular signaling peptides and proteins}}
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Latest revision as of 04:47, 31 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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View/Edit Human

Fibroblast growth factor 4 is a protein that in humans is encoded by the FGF4 gene.[1][2]

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway.[2]

Function

During embryonic development, the 21-kD protein FGF4 functions as a signaling molecule that is involved in many important processes.[3][4] Studies using Fgf4 gene knockout mice showed developmental defects in embryos both in vivo and in vitro, revealing that FGF4 facilitates the survival and growth of the inner cell mass during the postimplantation phase of development by acting as an autocrine or paracrine ligand.[3] FGFs produced in the apical ectodermal ridge (AER) are critical for the proper forelimb and hindlimb outgrowth.[5] FGF signaling in the AER is involved in regulating limb digit number and cell death in the interdigital mesenchyme.[6] When FGF signaling dynamics and regulatory processes are altered, postaxial polydactyly and cutaneous syndactyly, two phenotypic abnormalities collectively known as polysyndactyly, can occur in the limbs. Polysyndactyly is observed when an excess of Fgf4 is expressed in limb buds of wild-type mice. In mutant limb buds that do not express Fgf8, the expression of Fgf4 still results in polysyndactyly, but Fgf4 is also able to rescue all skeletal defects that arise from the lack of Fgf8. Therefore, the Fgf4 gene compensates for the loss of the Fgf8 gene, revealing that FGF4 and FGF8 perform similar functions in limb skeleton patterning and limb development.[6] Studies of zebrafish Fgf4 knockdown embryos demonstrated that when Fgf4 signaling is inhibited, randomized left-right patterning of the liver, pancreas, and heart takes place, showing that Fgf4 is a crucial gene involved in developing left-right patterning of visceral organs. Furthermore, unlike the role of FGF4 in limb development, FGF4 and FGF8 have distinct roles and function independently in the process of visceral organ left-right patterning.[7] Fgf signaling pathway has also been demonstrated to drive hindgut identity during gastrointestinal development, and the up regulation of the Fgf4 in pluripotent stem cell has been used to direct their differentiation for the generation of intestinal Organoids and tissues in vitro.[8]

References

  1. ↑ Galland F, Stefanova M, Lafage M, Birnbaum D (Jul 1992). "Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23". Cytogenetics and Cell Genetics. 60 (2): 114–6. doi:10.1159/000133316. PMID 1611909.
  2. ↑ 2.0 2.1 "Entrez Gene: FGF4 fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene)".
  3. ↑ 3.0 3.1 Feldman B, Poueymirou W, Papaioannou VE, DeChiara TM, Goldfarb M (Jan 1995). "Requirement of FGF-4 for postimplantation mouse development". Science. 267 (5195): 246–9. doi:10.1126/science.7809630. PMID 7809630.
  4. ↑ Yuan H, Corbi N, Basilico C, Dailey L (Nov 1995). "Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3". Genes & Development. 9 (21): 2635–45. doi:10.1101/gad.9.21.2635. PMID 7590241.
  5. ↑ Boulet AM, Moon AM, Arenkiel BR, Capecchi MR (Sep 2004). "The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth". Developmental Biology. 273 (2): 361–72. doi:10.1016/j.ydbio.2004.06.012. PMID 15328019.
  6. ↑ 6.0 6.1 Lu P, Minowada G, Martin GR (Jan 2006). "Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function". Development. 133 (1): 33–42. doi:10.1242/dev.02172. PMID 16308330.
  7. ↑ Yamauchi H, Miyakawa N, Miyake A, Itoh N (Aug 2009). "Fgf4 is required for left-right patterning of visceral organs in zebrafish". Developmental Biology. 332 (1): 177–85. doi:10.1016/j.ydbio.2009.05.568. PMID 19481538.
  8. ↑ Lancaster MA, Knoblich JA (2014). "Organogenesis in a dish: modeling development and disease using organoid technologies". Science. 345 (6194): 1247125. doi:10.1126/science.1247125. PMID 25035496.

Further reading

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