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]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 288 aminokiselina, а molekulska težina 30.770 Da.[9]
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
urediKao 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
urediPokazalo 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
urediReference
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Dopunska literatura
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Vanjski linkovi
uredi- 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.