FGF2, znan i kao osnovni fibroblastni faktor rasta (bFGF) i FGF-β, jest faktor rasta, signalni protein koji je kod ljudi kodiran genom FGF2 sa hromosoma 4.[5][6] Veže se za i vrši efekte preko specifičnih proteina receptora faktora rasta fibroblasta (FGFR) , koji su sami po sebi porodica blisko povezanih molekula. Faktor rasta fibroblasta je prvi put prečišćen 1975. godine; ubrzo nakon toga izolovane su tri varijante: osnovni FGF (FGF2); heparin-vezujući faktor rasta-2; i faktor rasta endotelnih ćelija-2. Sekvenciranje gena je otkrilo da je ova grupa isti protein FGF2 i da je član porodice proteina faktora rasta fibroblasta.[7][8]

FGF2
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1BAS, 1BFB, 1BFC, 1BFF, 1BFG, 1BLA, 1BLD, 1CVS, 1EV2, 1FGA, 1FQ9, 1II4, 1IIL, 2BFH, 2FGF, 2M49, 4FGF, 4OEE, 4OEF, 4OEG

Identifikatori
AliasiFGF2
Vanjski ID-jeviOMIM: 134920 MGI: 95516 HomoloGene: 1521 GeneCards: FGF2
Lokacija gena (čovjek)
Hromosom 4 (čovjek)
Hrom.Hromosom 4 (čovjek)[1]
Hromosom 4 (čovjek)
Genomska lokacija za FGF2
Genomska lokacija za FGF2
Bend4q28.1Početak122,826,708 bp[1]
Kraj122,898,236 bp[1]
Lokacija gena (miš)
Hromosom 3 (miš)
Hrom.Hromosom 3 (miš)[2]
Hromosom 3 (miš)
Genomska lokacija za FGF2
Genomska lokacija za FGF2
Bend3 B|3 18.41 cMPočetak37,402,495 bp[2]
Kraj37,464,257 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija cytokine activity
heparin binding
fibroblast growth factor receptor binding
GO:0001948, GO:0016582 vezivanje za proteine
nuclear receptor coactivator activity
chemoattractant activity
growth factor activity
protein tyrosine kinase activity
phosphatidylinositol-4,5-bisphosphate 3-kinase activity
1-phosphatidylinositol-3-kinase activity
receptor-receptor interaction
integrin binding
Ćelijska komponenta extracellular region
jedro
Vanćelijsko
Biološki proces release of sequestered calcium ion into cytosol
Ćelijska diferencijacija
negative regulation of fibroblast migration
hyaluronan catabolic process
positive regulation of endothelial cell proliferation
positive regulation of MAP kinase activity
negative regulation of blood vessel endothelial cell migration
positive regulation of endothelial cell chemotaxis to fibroblast growth factor
somatic stem cell population maintenance
positive regulation of phospholipase C activity
extracellular matrix organization
Zarastanje rana
negative regulation of cell death
regulation of angiogenesis
nervous system development
cell migration involved in sprouting angiogenesis
MAPK cascade
positive regulation of angiogenesis
positive regulation of phosphatidylinositol 3-kinase activity
GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
Hemotaksija
fibroblast growth factor receptor signaling pathway
chondroblast differentiation
multicellular organism development
growth factor dependent regulation of skeletal muscle satellite cell proliferation
branching involved in ureteric bud morphogenesis
positive regulation of cardiac muscle cell proliferation
embryonic morphogenesis
Angiogeneza
positive regulation of cell fate specification
animal organ morphogenesis
regulation of endothelial cell chemotaxis to fibroblast growth factor
phosphatidylinositol biosynthetic process
inositol phosphate biosynthetic process
negative regulation of wound healing
Ras protein signal transduction
positive regulation of cell division
GO:0072468 Transdukcija signala
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
positive chemotaxis
phosphatidylinositol phosphate biosynthetic process
peptidyl-tyrosine phosphorylation
positive regulation of sprouting angiogenesis
positive regulation of cell population proliferation
phosphatidylinositol-3-phosphate biosynthetic process
stem cell proliferation
regulation of signaling receptor activity
positive regulation of protein kinase B signaling
cytokine-mediated signaling pathway
positive regulation of blood vessel endothelial cell migration
positive regulation of ERK1 and ERK2 cascade
positive regulation of vascular associated smooth muscle cell proliferation
positive regulation of vascular endothelial cell proliferation
positive regulation of cell migration involved in sprouting angiogenesis
paracrine signaling
positive regulation of DNA biosynthetic process
positive regulation of endothelial cell chemotaxis
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_002006
NM_001361665

NM_008006

RefSeq (bjelančevina)

NP_001997
NP_001348594

NP_032032

Lokacija (UCSC)Chr 4: 122.83 – 122.9 MbChr 3: 37.4 – 37.46 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 288 aminokiselina, а molekulska težina 30.770 Da.[9]

1020304050
MVGVGGGDVEDVTPRPGGCQISGRGARGCNGIPGAAAWEAALPRRRPRRH
PSVNPRSRAAGSPRTRGRRTEERPSGSRLGDRGRGRALPGGRLGGRGRGR
APERVGGRGRGRGTAAPRAAPAARGSRPGPAGTMAAGSITTLPALPEDGG
SGAFPPGHFKDPKRLYCKNGGFFLRIHPDGRVDGVREKSDPHIKLQLQAE
ERGVVSIKGVCANRYLAMKEDGRLLASKCVTDECFFFERLESNNYNTYRS
RKYTSWYVALKRTGQYKLGSKTGPGQKAILFLPMSAKS

Function

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Kao i drugi članovi porodice FGF, osnovni faktor rasta fibroblasta ima široke mitogene aktivnosti i aktivnosti preživljavanja ćelija i angažirfan je u razne biološke procese, uključujući razvoj embriona, rast ćelije, morfogenezu, rfegeneraciju, rast i invaziju tumora.

U normalnom tkivu, bFGF je prisutan u baznoj membrani i u subendotelijalnom vanćelijskom matriksu krvnih sudova. Ostaje vezan za membranu sve dok ne postoji signalni peptid.

Pretpostavlja se da, kako tokom zacijeljelivanja rana normalnih tkiva i razvoja tumora, djelovanje heparan-sulfat-razgrađujućeg enzima aktivira bFGF, čime se posreduje u formiranju novog krvnog suda, proces poznat kao angiogeneza.

Osim toga, sintetiziraju ga i luče ljudski adipociti, a koncentracija FGF2 korelira s BMI u uzorcima krvi. Također se pokazalo da djeluje na preosteoblasti –u obliku povećane proliferacije –nakon vezivanja za receptor faktora rasta fibroblasta 1 i aktivacije fosfoinozitida 3 kinaza.[10]

U preliminarnim studijama na životinjama, pokazalo se da FGF2 štiti srce od ozljeda povezanih sa srčanim udarom, smanjujući smrt tkiva i promovirajući poboljšanu funkciju nakon reperfuzije.[11]

Nedavni dokazi su pokazali da niski nivoi FGF2 imaju ključnu ulogu u učestalosti pretjerane anksioznosti.[12]

Dodatno, FGF2 je kritična komponenta medija za kulturu ljudskih ih embrionskih matičnih ćelija; faktor rasta je neophodan da ćelije ostanu u nediferenciranom stanju, iako su mehanizmi pomoću kojih to čini slabo definirani. Pokazalo se da indukuje ekspresiju gremlina za koju je poznato da inhibira indukciju diferencijacije pomoću koštanih morfogenetskih proteina.[13] Neophodan je u sistemima kulture ćelija zavisnih od hranjenja miša, kao i u hranilicama i sistemima kulture bez seruma.[14] FGF2, u kombinaciji sa BMP4, promovira diferencijaciju matičnih ćelija u mezodermne linije. Nakon diferencijacije, ćelije tretirane BMP4 i FGF2 općenito proizvode veće količine osteogena i hondrogena diferencijacije od netretiranih matičnih ćelija.[15] Međutim, niska koncentracija bFGF (10 ng/mL) može imati inhibitorni efekat na diferencijaciju osteoblasta.[16] The nuclear form of FGF2 functions in mRNA export[17]

FGF2 se prvenstveno sintetizira kao polipeptid od 155 aminokiselina, što rezultira proteinom od 18 kDa. Međutim, postoje četiri alternativna početna kodona koji pružaju N-terminalne ekstenzije od 41, 46, 55 ili 133 aminokiseline, što rezultira proteinima od 22 kDa (ukupno 196 aa), 22,5 kDa (ukupno 201 aa), 24 kDa (210 aa ukupno), odnosno 34 kDa (288 aa ukupno).[7] Općenito, oblik niske molekulne težine 155 aa/18 kDa (LMW) smatra se citoplazmatskim i može se lučiti iz ćelije, dok se oblici visoke molekulne težine (HMW) usmjeravaju na ćelijsko jedro.[18]

Interakcije

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Pokazalo se da osnovni faktor rasta fibroblasta ima interakcije sa kazein-kinazom 2, alfa 1,[19] RPL6,[20] ribosomski protein S19[21] i API5.[17]

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138685 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037225 - Ensembl, maj 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 (septembar 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. ^ Kim HS (1998). "Assignment1 of the human basic fibroblast growth factor gene FGF2 to chromosome 4 band q26 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 83 (1–2): 73. doi:10.1159/000015129. PMID 9925931. S2CID 33214466.
  7. ^ a b Florkiewicz RZ, Shibata F, Barankiewicz T, Baird A, Gonzalez AM, Florkiewicz E, Shah N (decembar 1991). "Basic fibroblast growth factor gene expression". Annals of the New York Academy of Sciences. 638 (1): 109–26. doi:10.1111/j.1749-6632.1991.tb49022.x. PMID 1785797. S2CID 45425517.
  8. ^ 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.
  9. ^ "UniProt, P09038" (jezik: engleski). Pristupljeno 27. 10. 2021.
  10. ^ Kühn MC, Willenberg HS, Schott M, Papewalis C, Stumpf U, Flohé S, Scherbaum WA, Schinner S (februar 2012). "Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation". Molecular and Cellular Endocrinology. 349 (2): 180–8. doi:10.1016/j.mce.2011.10.018. PMID 22040599. S2CID 2305986.
  11. ^ House SL, Bolte C, Zhou M, Doetschman T, Klevitsky R, Newman G, Schultz Jel J (decembar 2003). "Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia". Circulation. 108 (25): 3140–8. doi:10.1161/01.CIR.0000105723.91637.1C. PMID 14656920. S2CID 14251918.
  12. ^ Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H (maj 2009). "A new role for FGF2 as an endogenous inhibitor of anxiety". The Journal of Neuroscience. 29 (19): 6379–87. doi:10.1523/JNEUROSCI.4829-08.2009. PMC 2748795. PMID 19439615.
  13. ^ Pereira RC, Economides AN, Canalis E (decembar 2000). "Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts". Endocrinology. 141 (12): 4558–63. doi:10.1210/en.141.12.4558. PMID 11108268. Arhivirano s originala, 11. 7. 2012.
  14. ^ Liu Y, Song Z, Zhao Y, Qin H, Cai J, Zhang H, Yu T, Jiang S, Wang G, Ding M, Deng H (juli 2006). "A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells". Biochemical and Biophysical Research Communications. 346 (1): 131–9. doi:10.1016/j.bbrc.2006.05.086. PMID 16753134.
  15. ^ Lee TJ, Jang J, Kang S, Jin M, Shin H, Kim DW, Kim BS (januar 2013). "Enhancement of osteogenic and chondrogenic differentiation of human embryonic stem cells by mesodermal lineage induction with BMP-4 and FGF2 treatment". Biochemical and Biophysical Research Communications. 430 (2): 793–7. doi:10.1016/j.bbrc.2012.11.067. PMID 23206696.
  16. ^ Del Angel-Mosqueda C, Gutiérrez-Puente Y, López-Lozano AP, Romero-Zavaleta RE, Mendiola-Jiménez A, Medina-De la Garza CE, Márquez-M M, De la Garza-Ramos MA (septembar 2015). "Epidermal growth factor enhances osteogenic differentiation of dental pulp stem cells in vitro". Head & Face Medicine. 11: 29. doi:10.1186/s13005-015-0086-5. PMC 4558932. PMID 26334535.
  17. ^ a b Bong SM, Bae SH, Song B, Gwak H, Yang SW, Kim S, Nam S, Rajalingam K, Oh SJ, Kim TW, Park S, Jang H, Lee BI (juni 2020). "Regulation of mRNA Export Through API5 and Nuclear FGF2 Interaction". Nucleic Acids Research. 48 (11): 6340–6352. doi:10.1093/nar/gkaa335. PMC 7293033. PMID 32383752.
  18. ^ 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.
  19. ^ 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.
  20. ^ Shen B, Arese M, Gualandris A, Rifkin DB (novembar 1998). "Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107". Biochemical and Biophysical Research Communications. 252 (2): 524–8. doi:10.1006/bbrc.1998.9677. PMID 9826564.
  21. ^ Soulet F, Al Saati T, Roga S, Amalric F, Bouche G (novembar 2001). "Fibroblast growth factor-2 interacts with free ribosomal protein S19". Biochemical and Biophysical Research Communications. 289 (2): 591–6. doi:10.1006/bbrc.2001.5960. PMID 11716516.

Dopunska literatura

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Vanjski linkovi

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Šablon:Signalni protein