FGF2

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 PDB Pretraga 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
Aliasi	FGF2
Vanjski ID-jevi	OMIM: 134920 MGI: 95516 HomoloGene: 1521 GeneCards: FGF2
Lokacija gena (čovjek) Hrom. Hromosom 4 (čovjek)[1] Bend 4q28.1 Početak 122,826,708 bp[1] Kraj 122,898,236 bp[1]
Lokacija gena (miš) Hrom. Hromosom 3 (miš)[2] Bend 3 B|3 18.41 cM Početak 37,402,495 bp[2] Kraj 37,464,257 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
Vrste	Čovjek	Miš
Entrez	2247	14173
Ensembl	ENSG00000138685	ENSMUSG00000037225
UniProt	P09038	P15655
RefSeq (mRNK)	NM_002006 NM_001361665	NM_008006
RefSeq (bjelančevina)	NP_001997 NP_001348594	NP_032032
Lokacija (UCSC)	Chr 4: 122.83 – 122.9 Mb	Chr 3: 37.4 – 37.46 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Aminokiselinska sekvenca

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

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MVGVGGGDVE		DVTPRPGGCQ		ISGRGARGCN		GIPGAAAWEA		ALPRRRPRRH
PSVNPRSRAA		GSPRTRGRRT		EERPSGSRLG		DRGRGRALPG		GRLGGRGRGR
APERVGGRGR		GRGTAAPRAA		PAARGSRPGP		AGTMAAGSIT		TLPALPEDGG
SGAFPPGHFK		DPKRLYCKNG		GFFLRIHPDG		RVDGVREKSD		PHIKLQLQAE
ERGVVSIKGV		CANRYLAMKE		DGRLLASKCV		TDECFFFERL		ESNNYNTYRS
RKYTSWYVAL		KRTGQYKLGS		KTGPGQKAIL		FLPMSAKS

Function

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

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

• Angiogeneza
• Anksioznost
• Citokin
• Faktor rasta fibroblasta
• Faktor rasta
• Proteaza
• Receptor (biohemija)
• Transdukcija signala

Reference

1. GRCh38: Ensembl release 89: ENSG00000138685 - Ensembl, maj 2017
2. 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. 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. 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

• Ornitz DM, Itoh N (2001). "Fibroblast growth factors". Genome Biology. 2 (3): REVIEWS3005. doi:10.1186/gb-2001-2-3-reviews3005. PMC 138918. PMID 11276432.
• Orpana A, Salven P (februar 2002). "Angiogenic and lymphangiogenic molecules in hematological malignancies". Leukemia & Lymphoma. 43 (2): 219–24. doi:10.1080/10428190290005964. PMID 11999550. S2CID 21908151.
• Marie PJ, Debiais F, Haÿ E (2003). "Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling". Histology and Histopathology. 17 (3): 877–85. doi:10.14670/HH-17.877. PMID 12168799.
• Zhao XC, Zhang LM, Tong DY, An P, Jiang C, Zhao P, Chen WM, Wang J (mart 2013). "Propofol increases expression of basic fibroblast growth factor after transient cerebral ischemia in rats". Neurochemical Research. 38 (3): 530–7. doi:10.1007/s11064-012-0945-4. PMC 3574197. PMID 23247820.
• Vincent T, Saklatvala J (juni 2006). "Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage?". Biochemical Society Transactions. 34 (Pt 3): 456–7. doi:10.1042/BST0340456. PMID 16709186.
• Ribatti D, Vacca A, Rusnati M, Presta M (2007). "The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and its role in haematological malignancies". Cytokine & Growth Factor Reviews. 18 (3–4): 327–34. doi:10.1016/j.cytogfr.2007.04.011. PMID 17537668.
• Watson R, Anthony F, Pickett M, Lambden P, Masson GM, Thomas EJ (septembar 1992). "Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients". Biochemical and Biophysical Research Communications. 187 (3): 1227–31. doi:10.1016/0006-291X(92)90434-M. PMID 1417798.
• Zhu X, Komiya H, Chirino A, Faham S, Fox GM, Arakawa T, Hsu BT, Rees DC (januar 1991). "Three-dimensional structures of acidic and basic fibroblast growth factors". Science. 251 (4989): 90–3. doi:10.1126/science.1702556. PMID 1702556.
• Eriksson AE, Cousens LS, Weaver LH, Matthews BW (april 1991). "Three-dimensional structure of human basic fibroblast growth factor". Proceedings of the National Academy of Sciences of the United States of America. 88 (8): 3441–5. doi:10.1073/pnas.88.8.3441. PMC 51463. PMID 1707542.
• Ago H, Kitagawa Y, Fujishima A, Matsuura Y, Katsube Y (septembar 1991). "Crystal structure of basic fibroblast growth factor at 1.6 A resolution". Journal of Biochemistry. 110 (3): 360–3. doi:10.1093/oxfordjournals.jbchem.a123586. PMID 1769963.
• Zhang JD, Cousens LS, Barr PJ, Sprang SR (april 1991). "Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta". Proceedings of the National Academy of Sciences of the United States of America. 88 (8): 3446–50. doi:10.1073/pnas.88.8.3446. PMC 51464. PMID 1849658.
• Wu DQ, Kan MK, Sato GH, Okamoto T, Sato JD (septembar 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.
• Fukushima Y, Byers MG, Fiddes JC, Shows TB (1991). "The human basic fibroblast growth factor gene (FGFB) is assigned to chromosome 4q25". Cytogenetics and Cell Genetics. 54 (3–4): 159–60. doi:10.1159/000132983. PMID 2265560.
• Lafage-Pochitaloff M, Galland F, Simonetti J, Prats H, Mattei MG, Birnbaum D (1990). "The human basic fibroblast growth factor gene is located on the long arm of chromosome 4 at bands q26-q27". Oncogene Research. 5 (3): 241–4. PMID 2320377.
• Story MT, Esch F, Shimasaki S, Sasse J, Jacobs SC, Lawson RK (februar 1987). "Amino-terminal sequence of a large form of basic fibroblast growth factor isolated from human benign prostatic hyperplastic tissue". Biochemical and Biophysical Research Communications. 142 (3): 702–9. doi:10.1016/0006-291X(87)91471-9. PMID 2435284.
• Kurokawa T, Sasada R, Iwane M, Igarashi K (mart 1987). "Cloning and expression of cDNA encoding human basic fibroblast growth factor". FEBS Letters. 213 (1): 189–94. doi:10.1016/0014-5793(87)81489-8. PMID 2435575. S2CID 28111330.
• Prats H, Kaghad M, Prats AC, Klagsbrun M, Lélias JM, Liauzun P, Chalon P, Tauber JP, Amalric F, Smith JA (mart 1989). "High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons". Proceedings of the National Academy of Sciences of the United States of America. 86 (6): 1836–40. doi:10.1073/pnas.86.6.1836. PMC 286799. PMID 2538817.
• Florkiewicz RZ, Sommer A (juni 1989). "Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons". Proceedings of the National Academy of Sciences of the United States of America. 86 (11): 3978–81. doi:10.1073/pnas.86.11.3978. PMC 287371. PMID 2726761.
• Abraham JA, Whang JL, Tumolo A, Mergia A, Fiddes JC (1987). "Human basic fibroblast growth factor: nucleotide sequence, genomic organization, and expression in mammalian cells". Cold Spring Harbor Symposia on Quantitative Biology. 51 Pt 1: 657–68. doi:10.1101/sqb.1986.051.01.078. PMID 3472745.
• Sommer A, Brewer MT, Thompson RC, Moscatelli D, Presta M, Rifkin DB (april 1987). "A form of human basic fibroblast growth factor with an extended amino terminus". Biochemical and Biophysical Research Communications. 144 (2): 543–50. doi:10.1016/S0006-291X(87)80001-3. PMID 3579930.

Vanjski linkovi

• Basic Fibroblast Growth Factor na US National Library of Medicine Medical Subject Headings (MeSH)
• Lokacija ljudskog genoma FGF2 i stranica sa detaljima o genu FGF2 u UCSC Genome Browseru.

Šablon:Signalni protein