Fibroblast growth factor 1

This article is about fibroblast growth factor-1. For the internal ribosome entry site, see FGF-1 internal ribosome entry site (IRES).

FGF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4QO3, 1AXM, 1DJS, 1DZC, 1DZD, 1E0O, 1EVT, 1HKN, 1JQZ, 1JT3, 1JT4, 1JT5, 1JT7, 1JTC, 1JY0, 1K5U, 1K5V, 1M16, 1NZK, 1P63, 1PZZ, 1Q03, 1Q04, 1RG8, 1RML, 1RY7, 1YTO, 1Z2V, 1Z4S, 2AFG, 2AQZ, 2AXM, 2ERM, 2HW9, 2HWA, 2HWM, 2HZ9, 2K43, 2K4A, 2K8R, 2KI4, 2KI6, 2NTD, 2Q9X, 2RQ9, 3B9U, 3BA4, 3BA5, 3BA7, 3BAD, 3BAG, 3BAH, 3BAO, 3BAQ, 3BAU, 3BAV, 3BB2, 3CQA, 3CRG, 3CRH, 3CRI, 3CU1, 3FGM, 3FJ8, 3FJ9, 3FJA, 3FJB, 3FJC, 3FJD, 3FJE, 3FJF, 3FJH, 3FJI, 3FJJ, 3FJK, 3HOM, 3JUT, 3K1X, 3O3Q, 3OJ2, 3OJM, 3OJV, 3UD7, 3UD8, 3UD9, 3UDA, 4J23, 4Q91, 4Q9G, 4Q9P, 4QAL, 4QBC, 4QBV, 4QC4, 4XKI, 4YOL
Identifiers
Aliases	FGF1 , AFGF, ECGF, ECGF-beta, ECGFA, ECGFB, FGF-1, FGF-alpha, FGFA, GLIO703, HBGF-1, HBGF1, fibroblast growth factor 1
External IDs	OMIM: 131220; MGI: 95515; HomoloGene: 625; GeneCards: FGF1; OMA:FGF1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) [1] Band 5q31.3 Start 142,592,178 bp [1] End 142,698,070 bp [1]
Gene location (Mouse) Chr. Chromosome 18 (mouse) [2] Band 18 B3|18 20.74 cM Start 38,971,726 bp [2] End 39,062,525 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in glomerulus metanephric glomerulus inferior ganglion of vagus nerve corpus callosum optic nerve external globus pallidus internal globus pallidus medulla oblongata inferior olivary nucleus olfactory bulb Top expressed in deep cerebellar nuclei pontine nuclei medial vestibular nucleus habenula facial motor nucleus dorsal tegmental nucleus anterior horn of spinal cord right lung myocardium of ventricle right ventricle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function S100 protein binding protein binding growth factor activity protein tyrosine kinase activity phosphatidylinositol-4,5-bisphosphate 3-kinase activity fibroblast growth factor receptor binding integrin binding 1-phosphatidylinositol-3-kinase activity heparin binding Hsp70 protein binding Cellular component cytoplasm cytosol extracellular region cell cortex nucleolus nucleus extracellular space extracellular matrix Biological process cell differentiation cellular response to heat positive regulation of protein phosphorylation positive regulation of MAP kinase activity organ induction lung development positive regulation of epithelial cell proliferation anatomical structure morphogenesis positive regulation of intracellular signal transduction branch elongation involved in ureteric bud branching positive regulation of angiogenesis MAPK cascade multicellular organism development mesonephric epithelium development angiogenesis regulation of endothelial cell chemotaxis to fibroblast growth factor positive regulation of cholesterol biosynthetic process cell population proliferation positive regulation of cell division positive regulation of transcription by RNA polymerase II signal transduction phosphatidylinositol phosphate biosynthetic process peptidyl-tyrosine phosphorylation positive regulation of sprouting angiogenesis fibroblast growth factor receptor signaling pathway positive regulation of cell population proliferation phosphatidylinositol-3-phosphate biosynthetic process regulation of endothelial tube morphogenesis positive regulation of cell migration positive regulation of endothelial cell migration activation of protein kinase B activity regulation of signaling receptor activity positive regulation of protein kinase B signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2246 14164 Ensembl ENSG00000113578 ENSMUSG00000036585 UniProt P05230 P61148 RefSeq (mRNA) NM_000800 NM_001144892 NM_001144934 NM_001144935 NM_001257205 NM_001257206 NM_001257207 NM_001257208 NM_001257209 NM_001257210 NM_001257211 NM_001257212 NM_033136 NM_033137 NM_001354955 NM_001354956 NM_001354957 NM_001354958 NM_001354959 NM_001354961 NM_001354963 NM_001354964 NM_001354951 NM_001354952 NM_001354953 NM_001354954 NM_001354962 NM_010197 RefSeq (protein) NP_000791 NP_001138364 NP_001138406 NP_001138407 NP_001244134 NP_001244135 NP_001244136 NP_001244137 NP_001244138 NP_001244139 NP_001244140 NP_001244141 NP_149127 NP_149128 NP_001341884 NP_001341885 NP_001341886 NP_001341887 NP_001341888 NP_001341890 NP_001341892 NP_001341893 NP_001341880 NP_001341881 NP_001341882 NP_001341883 NP_001341891 NP_034327 Location (UCSC) Chr 5: 142.59 – 142.7 Mb Chr 18: 38.97 – 39.06 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fibroblast growth factor 1(FGF-1) also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the FGF1 gene. ^{[5] [6]} It is synthesized as a 155 amino acid polypeptide, whose mature form is a non-glycosylated 17-18 kDa protein. Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated acidic FGF, Heparin-binding growth factor-1, and Endothelial cell growth factor-1. ^[7] Gene sequencing revealed that this group was actually the same growth factor and that FGF1 was a member of a family of FGF proteins.

FGF-1 has no definitive signal sequence and thus is not secreted through classical pathways, but it does appear to form a disulfide linked dimer inside cells that associate with a complex of proteins at the cell membrane (including S100A13 and Syt1) which then help flip it through the membrane to the exterior of the cell. ^{[8] [9]} Once in the reducing conditions of the surrounding tissue, the dimer dissociates into monomeric FGF1 that can enter systemic circulation or be sequestered in tissues binding to heparan sulfate proteoglycans of the extracellular matrix. FGF1 can then bind to and exert its effects via specific fibroblast growth factor receptor (FGFR) proteins which themselves constitute a family of closely related molecules. ^[10]

In addition to its extracellular activity, FGF1 can also function intracellularly. The protein has a nuclear localization sequence (NLS) but the route that FGF1 takes to get to the nucleus is unclear and it appears that some sort of cell surface receptor binding is necessary, followed by its internalization and translocation to the nucleus whereupon it can interact with nuclear isoforms of FGFRs. ^[10] This is different from FGF2 which also can activate nuclear FGFRs but has splicing variants of the protein that never leave the cell and go directly to the nucleus.^{[ citation needed ]}

Function

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 protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described. ^[11]

FGF1 is multifunctional with many reported effects. For one example, in mice with diet-induced diabetes that is an experimental equivalent of type 2 diabetes in humans, a single injection of the FGF1 protein is enough to restore blood sugar levels to a healthy range for > 2 days. ^[12]

Interactions

FGF1 has been shown to interact with:

• CSNK2A2 ^[13]
• CSNK2B ^[13]
• CSNK2A1 ^[13]
• FIBP ^[14]
• FGFR1 ^{[15] [16]}
• FGFR2 ^{[16] [17] [18]}
• FGFR3 ^{[16] [19]}
• FGFR4 ^{[20] [21]}
• HSPA9 ^[22] and
• S100A13 ^{[9] [23] [24]}
• Synaptotagmin 1 (SYT1) ^{[9] [23]}

See also

• Fibroblast growth factor

References

1. GRCh38: Ensembl release 89: ENSG00000113578 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000036585 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J (September 1990). "Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors". The EMBO Journal. 9 (9): 2685–92. doi:10.1002/j.1460-2075.1990.tb07454.x. PMC   551973 . PMID   1697263.
6. Jaye M, Howk R, Burgess W, Ricca GA, Chiu IM, Ravera MW, O'Brien SJ, Modi WS, Maciag T, Drohan WN (August 1986). "Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization". Science. 233 (4763): 541–5. Bibcode:1986Sci...233..541J. doi:10.1126/science.3523756. PMID   3523756.
7. Burgess WH, Maciag T (1989). "The heparin-binding (fibroblast) growth factor family of proteins". Annual Review of Biochemistry. 58: 575–606. doi:10.1146/annurev.bi.58.070189.003043. PMID   2549857.
8. Tarantini F, Gamble S, Jackson A, Maciag T (December 1995). "The cysteine residue responsible for the release of fibroblast growth factor-1 residues in a domain independent of the domain for phosphatidylserine binding". The Journal of Biological Chemistry. 270 (49): 29039–42. doi: 10.1074/jbc.270.49.29039 . PMID   7493920.
9. Prudovsky I, Bagala C, Tarantini F, Mandinova A, Soldi R, Bellum S, Maciag T (July 2002). "The intracellular translocation of the components of the fibroblast growth factor 1 release complex precedes their assembly prior to export". The Journal of Cell Biology. 158 (2): 201–8. doi:10.1083/jcb.200203084. PMC   2173119 . PMID   12135982.
10. Coleman SJ, Bruce C, Chioni AM, Kocher HM, Grose RP (August 2014). "The ins and outs of fibroblast growth factor receptor signalling". Clinical Science. 127 (4): 217–31. doi:10.1042/CS20140100. PMID   24780002.
11. "Entrez Gene: FGF1 fibroblast growth factor 1 (acidic)".
12. Suh JM, Jonker JW, Ahmadian M, Goetz R, Lackey D, Osborn O, Huang Z, Liu W, Yoshihara E, van Dijk TH, Havinga R, Fan W, Yin YQ, Yu RT, Liddle C, Atkins AR, Olefsky JM, Mohammadi M, Downes M, Evans RM (September 2014). "Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer". Nature. 513 (7518): 436–9. Bibcode:2014Natur.513..436S. doi:10.1038/nature13540. PMC   4184286 . PMID   25043058.*Lay summary in: "One injection stops diabetes in its tracks". Salk Institute. July 16, 2014.
13. Skjerpen CS, Nilsen T, Wesche J, Olsnes S (August 2002). "Binding of FGF-1 variants to protein kinase CK2 correlates with mitogenicity". The EMBO Journal. 21 (15): 4058–69. doi:10.1093/emboj/cdf402. PMC   126148 . PMID   12145206.
14. Kolpakova E, Wiedłocha A, Stenmark H, Klingenberg O, Falnes PO, Olsnes S (November 1998). "Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor". The Biochemical Journal. 336 (1): 213–22. doi:10.1042/bj3360213. PMC   1219860 . PMID   9806903.
15. Schlessinger J, Plotnikov AN, Ibrahimi OA, Eliseenkova AV, Yeh BK, Yayon A, Linhardt RJ, Mohammadi M (September 2000). "Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization". Molecular Cell. 6 (3): 743–50. doi: 10.1016/s1097-2765(00)00073-3 . PMID   11030354.
16. Santos-Ocampo S, Colvin JS, Chellaiah A, Ornitz DM (January 1996). "Expression and biological activity of mouse fibroblast growth factor-9". The Journal of Biological Chemistry. 271 (3): 1726–31. doi: 10.1074/jbc.271.3.1726 . PMID   8576175.
17. Stauber DJ, DiGabriele AD, Hendrickson WA (January 2000). "Structural interactions of fibroblast growth factor receptor with its ligands". Proceedings of the National Academy of Sciences of the United States of America. 97 (1): 49–54. Bibcode:2000PNAS...97...49S. doi: 10.1073/pnas.97.1.49 . PMC   26614 . PMID   10618369.
18. Pellegrini L, Burke DF, von Delft F, Mulloy B, Blundell TL (October 2000). "Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin". Nature. 407 (6807): 1029–34. Bibcode:2000Natur.407.1029P. doi:10.1038/35039551. PMID   11069186. S2CID   4418272.
19. Chellaiah A, Yuan W, Chellaiah M, Ornitz DM (December 1999). "Mapping ligand binding domains in chimeric fibroblast growth factor receptor molecules. Multiple regions determine ligand binding specificity". The Journal of Biological Chemistry. 274 (49): 34785–94. doi: 10.1074/jbc.274.49.34785 . PMID   10574949.
20. Loo BB, Darwish KK, Vainikka SS, Saarikettu JJ, Vihko PP, Hermonen JJ, Goldman AA, Alitalo KK, Jalkanen MM (May 2000). "Production and characterization of the extracellular domain of recombinant human fibroblast growth factor receptor 4". The International Journal of Biochemistry & Cell Biology. 32 (5): 489–97. doi:10.1016/S1357-2725(99)00145-4. PMID   10736564.
21. Kan M, Wu X, Wang F, McKeehan WL (May 1999). "Specificity for fibroblast growth factors determined by heparan sulfate in a binary complex with the receptor kinase". The Journal of Biological Chemistry. 274 (22): 15947–52. doi: 10.1074/jbc.274.22.15947 . PMID   10336501.
22. Mizukoshi E, Suzuki M, Loupatov A, Uruno T, Hayashi H, Misono T, Kaul SC, Wadhwa R, Imamura T (October 1999). "Fibroblast growth factor-1 interacts with the glucose-regulated protein GRP75/mortalin". The Biochemical Journal. 343 (2): 461–6. doi:10.1042/0264-6021:3430461. PMC   1220575 . PMID   10510314.
23. Mouta Carreira C, LaVallee TM, Tarantini F, Jackson A, Lathrop JT, Hampton B, Burgess WH, Maciag T (August 1998). "S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro". The Journal of Biological Chemistry. 273 (35): 22224–31. doi: 10.1074/jbc.273.35.22224 . hdl: 2158/26736 . PMID   9712836.
24. Landriscina M, Bagalá C, Mandinova A, Soldi R, Micucci I, Bellum S, Prudovsky I, Maciag T (July 2001). "Copper induces the assembly of a multiprotein aggregate implicated in the release of fibroblast growth factor 1 in response to stress". The Journal of Biological Chemistry. 276 (27): 25549–57. doi: 10.1074/jbc.M102925200 . PMID   11432880.

Further reading

• Yu YL, Kha H, Golden JA, Migchielsen AA, Goetzl EJ, Turck CW (April 1992). "An acidic fibroblast growth factor protein generated by alternate splicing acts like an antagonist". The Journal of Experimental Medicine. 175 (4): 1073–80. doi:10.1084/jem.175.4.1073. PMC   2119192 . PMID   1372643.
• Chiu IM, Wang WP, Lehtoma K (May 1990). "Alternative splicing generates two forms of mRNA coding for human heparin-binding growth factor 1". Oncogene. 5 (5): 755–62. PMID   1693186.
• Zhu X, Komiya H, Chirino A, Faham S, Fox GM, Arakawa T, Hsu BT, Rees DC (January 1991). "Three-dimensional structures of acidic and basic fibroblast growth factors". Science. 251 (4989): 90–3. Bibcode:1991Sci...251...90Z. doi:10.1126/science.1702556. PMID   1702556.
• Wang WP, Quick D, Balcerzak SP, Needleman SW, Chiu IM (September 1991). "Cloning and sequence analysis of the human acidic fibroblast growth factor gene and its preservation in leukemia patients". Oncogene. 6 (9): 1521–9. PMID   1717925.
• Wu DQ, Kan MK, Sato GH, Okamoto T, Sato JD (September 1991). "Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors". The Journal of Biological Chemistry. 266 (25): 16778–85. doi: 10.1016/S0021-9258(18)55368-0 . PMID   1885605.
• Crumley G, Dionne CA, Jaye M (August 1990). "The gene for human acidic fibroblast growth factor encodes two upstream exons alternatively spliced to the first coding exon". Biochemical and Biophysical Research Communications. 171 (1): 7–13. doi:10.1016/0006-291X(90)91348-V. PMID   2393407.
• Harper JW, Strydom DJ, Lobb RR (July 1986). "Human class 1 heparin-binding growth factor: structure and homology to bovine acidic brain fibroblast growth factor". Biochemistry. 25 (14): 4097–103. doi:10.1021/bi00362a017. PMID   2427112.
• Winkles JA, Friesel R, Burgess WH, Howk R, Mehlman T, Weinstein R, Maciag T (October 1987). "Human vascular smooth muscle cells both express and respond to heparin-binding growth factor I (endothelial cell growth factor)". Proceedings of the National Academy of Sciences of the United States of America. 84 (20): 7124–8. Bibcode:1987PNAS...84.7124W. doi: 10.1073/pnas.84.20.7124 . PMC   299242 . PMID   2444975.
• Wang WP, Lehtoma K, Varban ML, Krishnan I, Chiu IM (June 1989). "Cloning of the gene coding for human class 1 heparin-binding growth factor and its expression in fetal tissues". Molecular and Cellular Biology. 9 (6): 2387–95. doi:10.1128/mcb.9.6.2387. PMC   362312 . PMID   2474753.
• Mergia A, Tischer E, Graves D, Tumolo A, Miller J, Gospodarowicz D, Abraham JA, Shipley GD, Fiddes JC (November 1989). "Structural analysis of the gene for human acidic fibroblast growth factor". Biochemical and Biophysical Research Communications. 164 (3): 1121–9. doi:10.1016/0006-291X(89)91785-3. PMID   2590193.
• Gimenez-Gallego G, Conn G, Hatcher VB, Thomas KA (July 1986). "The complete amino acid sequence of human brain-derived acidic fibroblast growth factor". Biochemical and Biophysical Research Communications. 138 (2): 611–7. doi:10.1016/S0006-291X(86)80540-X. PMID   3527167.
• Gautschi P, Fràter-Schröder M, Böhlen P (August 1986). "Partial molecular characterization of endothelial cell mitogens from human brain: acidic and basic fibroblast growth factors". FEBS Letters. 204 (2): 203–7. Bibcode:1986FEBSL.204..203G. doi: 10.1016/0014-5793(86)80812-2 . PMID   3732516. S2CID   22617694.
• Gautschi-Sova P, Müller T, Böhlen P (November 1986). "Amino acid sequence of human acidic fibroblast growth factor". Biochemical and Biophysical Research Communications. 140 (3): 874–80. doi:10.1016/0006-291X(86)90716-3. PMID   3778488.
• Gimenez-Gallego G, Conn G, Hatcher VB, Thomas KA (March 1986). "Human brain-derived acidic and basic fibroblast growth factors: amino terminal sequences and specific mitogenic activities". Biochemical and Biophysical Research Communications. 135 (2): 541–8. doi:10.1016/0006-291X(86)90028-8. PMID   3964259.
• Zhao XM, Yeoh TK, Hiebert M, Frist WH, Miller GG (November 1993). "The expression of acidic fibroblast growth factor (heparin-binding growth factor-1) and cytokine genes in human cardiac allografts and T cells". Transplantation. 56 (5): 1177–82. doi: 10.1097/00007890-199311000-00025 . PMID   7504343.
• Pineda-Lucena A, Jiménez MA, Nieto JL, Santoro J, Rico M, Giménez-Gallego G (September 1994). "1H-NMR assignment and solution structure of human acidic fibroblast growth factor activated by inositol hexasulfate". Journal of Molecular Biology. 242 (1): 81–98. doi:10.1006/jmbi.1994.1558. PMID   7521397.
• Chotani MA, Payson RA, Winkles JA, Chiu IM (February 1995). "Human fibroblast growth factor 1 gene expression in vascular smooth muscle cells is modulated via an alternate promoter in response to serum and phorbol ester". Nucleic Acids Research. 23 (3): 434–41. doi:10.1093/nar/23.3.434. PMC   306694 . PMID   7533902.
• Opalenik SR, Shin JT, Wehby JN, Mahesh VK, Thompson JA (July 1995). "The HIV-1 TAT protein induces the expression and extracellular appearance of acidic fibroblast growth factor". The Journal of Biological Chemistry. 270 (29): 17457–67. doi: 10.1074/jbc.270.29.17457 . PMID   7542239.
• Myers RL, Payson RA, Chotani MA, Deaven LL, Chiu IM (February 1993). "Gene structure and differential expression of acidic fibroblast growth factor mRNA: identification and distribution of four different transcripts". Oncogene. 8 (2): 341–9. PMID   7678925.