Receptor faktora rasta

Epidermni faktor rasta (crveno) i njegov receptor (plavo). Neaktivni oblik (lijevo) dimerizira se kada se veže za hormon (desno). Ćelijska membrana prikazana je sivom bojom.
(PDB: 2GS6, 1N8Z, 1YY9, 1EGF)

Receptor faktora rasta je receptor koji se vezuje za faktor rasta.[1] Receptori faktora rasta su prva stanica u ćelijama gdje počinje signalna kaskada za ćelijsku diferencijaciju i proliferaciju. Faktori rasta, koji su ligandi za vezanja za receptor, početni su korak u aktiviranju receptora faktora rasta i signaliziraju ćeliji da raste i/ili se dijeli.[2] Ovi receptori mogu koristiti JAK/STAT, Map-kinazne i PI3-kinazne puteve.[3]

Većina receptora faktora rasta sastoji se od receptorske tirozin-kinaze (RTK). Postoje tri dominantna tipa receptora koji su ekskluzivni za istraživanje: receptor epidermnog faktora rasta, nutrotrofinski receptor i inzulinoliki receptori.[4] Svi receptori faktora rasta vezani su za membranu i sastoje se od tri opća proteinska domena: vanćelijski, transmembranski i citoplazmatski.[5] The extracellular domain region is where a ligand may bind, usually with very high specificity.[6] U RTKs, vezivanje liganda za mjesto vezanja vanćelijskog liganda dovodi do autofosforilacije ostataka tirozina u unutarćelijskom domenu.[7] Ove fosforilacije omogućavaju drugim unutarćelijskim proteinima da se vežu na fosfotirozin-vezujući domen, što rezultira nizom fizioloških odgovora unutar ćelije.[7]

Klinički značaj

Istraživanja u današnjem društvu fokusiraju se na receptore faktora rasta kako bi se precizno odredilo liječenje raka. Receptori epidermnog faktora rasta su u velikoj mjeri uključeni u onkogenu aktivnost.[8] Kada se faktori rasta vežu za svoj receptor, u ćeliji se javlja put transdukcije signala, kako bi se osigurao da ćelija radi. Međutim, u ćelijama raka, put se možda nikada neće uključiti ili isključiti.[8] Nadalje, kod određenih karcinoma, receptori (kao što je RTKs) često se primjećuju kao preeksprimirani, što odgovara nekontroliranoj proliferaciji i diferencijaciji ćelija.[9] Iz istog razloga, trozinski receptora često su cilj terapije kancera.[9]

Reference

  1. ^ Growth Factor Receptors na US National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ "Growth Factor Receptors | Tocris Bioscience". Tocris Bioscience. Pristupljeno 30. 3. 2016.
  3. ^ A. V. Hoffbrand; P. A. H. Moss; J. E. Pettit (2006). Essential haematology. Wiley-Blackwell. str. 6–. ISBN 978-1-4051-3649-5. Pristupljeno 28. 11. 2010.
  4. ^ McInnes, Campbell; Sykes, Brian D. (1997). "Growth factor receptors: Structure, mechanism, and drug discovery". Peptide Science (jezik: engleski). 43 (5): 339–366. doi:10.1002/(SICI)1097-0282(1997)43:5<339::AID-BIP2>3.0.CO;2-W. ISSN 1097-0282. PMID 9566117.
  5. ^ Goodman, Steven R., ured. (1. 1. 2008), "Chapter 7 - Intercellular Signaling", Medical Cell Biology (Third Edition) (jezik: engleski), Academic Press, str. 227–248, ISBN 978-0-12-370458-0, pristupljeno 29. 4. 2020
  6. ^ Kouvidi, Katerina; Nikitovic, Dragana; Berdiaki, Aikaterini; Tzanakakis, George N. (1. 1. 2014), Simpson, Melanie A.; Heldin, Paraskevi (ured.), "Chapter Twelve - Hyaluronan/RHAMM Interactions in Mesenchymal Tumor Pathogenesis: Role of Growth Factors", Advances in Cancer Research, Hyaluronan Signaling and Turnover (jezik: engleski), Academic Press, 123, str. 319–349, pristupljeno 29. 4. 2020
  7. ^ a b Trenker, Raphael; Jura, Natalia (1. 4. 2020). "Receptor tyrosine kinase activation: From the ligand perspective". Current Opinion in Cell Biology (jezik: engleski). 63: 174–185. doi:10.1016/j.ceb.2020.01.016. ISSN 0955-0674. PMID 32114309.
  8. ^ a b Sasaki, Takamitsu; Hiroki, Kuniyasu; Yamashita, Yuichi (2013). "The Role of Epidermal Growth Factor Receptor in Cancer Metastasis and Microenvironment". BioMed Research International. 2013: 546318. doi:10.1155/2013/546318. ISSN 2314-6133. PMC 3748428. PMID 23986907.
  9. ^ a b Bennasroune, Amar; Gardin, Anne; Aunis, Dominique; Crémel, Gérard; Hubert, Pierre (1. 4. 2004). "Tyrosine kinase receptors as attractive targets of cancer therapy". Critical Reviews in Oncology/Hematology (jezik: engleski). 50 (1): 23–38. doi:10.1016/j.critrevonc.2003.08.004. ISSN 1040-8428. PMID 15094157.

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