FGF1
(Preusmjereno sa AFGF)
FGF1, znan i kao kiseli faktor rasta fibroblasta (aFGF), jest faktor rasta i signalni protein koji je kod ljudi kodiran genom FGF1 sa hromosoma 5.[5][6]
Sintetizira se kao polipeptid od 155 aminokiselina, čiji je zreli oblik neglikoziliran protein od 17-18 kDa. Protein faktora rasta fibroblasta je prvi put prečišćen 1975. godine, ali su ubrzo nakon toga drugi, koristeći različite uvjete, izolirali kiseli FGF, faktor rasta koji veže heparin-1 i faktor rasta endotelnih ćelija-1.[7] Sekvenciranje gena otkrilo je da je ova grupa zapravo isti faktor rasta i da je FGF1 bio član proteina porodice FGF.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 155 aminokiselina, а molekulska težina 17.460 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAEGEITTFT | ALTEKFNLPP | GNYKKPKLLY | CSNGGHFLRI | LPDGTVDGTR | ||||
| DRSDQHIQLQ | LSAESVGEVY | IKSTETGQYL | AMDTDGLLYG | SQTPNEECLF | ||||
| LERLEENHYN | TYISKKHAEK | NWFVGLKKNG | SCKRGPRTHY | GQKAILFLPL | ||||
| PVSSD |
Funkcija
urediČlanovi porodice FGF imaju široku mitogenu i aktivnost preživljavanja ćelija i uključeni su u različite biološke procese, uključujući embrionsk i razvoj, rast ćelija, morfogenezu, popravak tkiva, rast i invaziju tumora. Ovaj protein funkcionira kao modifikator migracije i proliferacije endotelnih ćelija, kao i angiogeni faktor. Djeluje kao mitogen za različite mezodermno izvedene ćelije i iz neuroektoderm in vitro, pa se smatra da je uključen u organogenezu. Opisane su tri alternativno prerađene varijante transkripta, koje kodiraju različite izoforme.[9]
FGF1 je multifunkcionalan sa mnogo prijavljenih efekata. Naprimjer, kod miševa s dijabetesom uzrokovanim ishranom, koji je eksperimentalni ekvivalent dijabetesa tipa 2 kod ljudi, jedna injekcija proteina FGF1 dovoljna je za vraćanje razine šećera u krvi u zdravi raspon za > 2 dana.[10]
FGF-1 nema definitivnu signalnu sekvencu pa se stoga ne izlučuje klasičnim putevima, ali čini se da tvori disulfidom povezan dimer unutar ćelija koji se povezuje sa kompleksom proteina na ćelijskoj membrani (uključujući S100A13 i Syt1) koji ga zatim pomažu prebaciti kroz membranu do vanjske strane ćelije.[11][12] U redukcijskim uvjetima okolnog tkiva, dimer se disocira na monomerni FGF1 koji može ući u sistemsku cirkulaciju ili se sekvestrirati u tkivima, gdje se vezuju za heparan sulfatni proteoglikan iz vanćelijskog matriksa . FGF1 se tada može vezati i djelovati putem specifičnih receptora faktora rasta fibroblasta (FGFR), proteina koji sami čine porodicu blisko povezanih molekula.[13]
Osim vanćelijske aktivnosti, FGF1 može djelovati i unutar ćelija. Protein ima jedarnu sekvencu (NLS), ali put kojim FGF1 prolazi do jedra nije jasan i čini se da je potreban neki tip vezanja receptora na površini ćdlije, nakon čega slijedi njegova internalizacija i translokacija u jedro pri čemu može stupiti u interakciju s jedarnim izoformama FGFR-a.[13] Ovo se razlikuje od FGF2 koji također može aktivirati jedarne FGFR-e, ali ima varijante transkripta proteina koje nikada ne napuštaju ćeliju i odlaze direktno do jedra.
Interakcije
urediPokazalo se da FGF1 stupa u interakcije sa:
Također pogledajte
urediReference
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Dopunska literatura
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