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Flavonoids as Inhibitors of Lck and Fyn Kinases

Croatian International Relations Review

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Title Flavonoids as Inhibitors of Lck and Fyn Kinases
Flavonoidi kao inhibitori Lck i Fyn kinaza
 
Creator Čalić, Maja
Jelić, Dubravko
Antolović, Roberto
Nujić, Krunoslav
Marjanović, Nikola
Stupin Polančec, Darija
Vikić-Topić, Smiljka
Verbanac, Donatella
 
Subject tyrosine kinases; Lck; Fyn; flavonoids; ELISA
 
Description Phosphorylation of tyrosine residues constitutes a unique signaling pathway involved in regulation of most cellular processes responding to different extracellular stimuli. The enzymes that carry out this modification are tyrosine kinases. These enzymes enable the transfer of γ-phosphate from ATP to the phenol –OH group of tyrosine on protein substrates. Development of specific and potent protein kinase inhibitors is important not only for treatment of diseases, but also as a tool to investigate the physiological roles of protein kinases. Flavonoids are biologically active polyphenol compounds naturally occurring in many plants. They are recognized as inhibitors of Fyn and Lck protein kinases, two representatives of the Src family of non receptor kinases involved in T-cell signaling transport. In the described experiments, the inhibitory activity of flavonoids on Fyn and Lck kinases was monitored by the ELISA method. Myricetin showed the highest inhibitory effect, and no ATP-competitive mechanism of inhibition was observed on Fyn tyrosine kinase. The affinity of human Fyn and Lck for two different substrates, polypeptide polymer Poly Glu:Tyr (4:1) and peptide M3-01, was also tested.
Tirozinska fosforilacija predstavlja jedinstveni mehanizam prijenosa signala primljenoga iz okoline do stanič ne jezgre koja će odgovoriti na podražaj. Velika skupina enzima odgovorna za provo|enje ove modifikacije poznata je pod jedinstvenim nazivom tirozinske kinaze. One omogućuju prijenos -fosfata ATP-a na –OH skupinu tirozina supstrata. Lck i Fyn su dvije nereceptorske Src tirozinske kinaze, koje su važne komponente regulacije aktivnosti T-limfocita. Rezultati ispitivanja flavonoida, biološki aktivnih polifenolnih spojeva prirodno prisutnih u mnogim biljkama, upućuju na njihov inhibitorni učinak na proteinske kinaze Fyn i Lck. Najveću inhibiciju pokazao je miricetin, a pri ispitivanju mehanizma inhibicije Fyn kinaze nije ustanovljena kompeticija s ATP-om. Ispitivanje potencijalne inhibicijske aktivnosti flavonoidnih spojeva prema kinazama Fyn i Lck, provedeno je ELISA metodom. Pri tome je uspore|en afinitet ispitivanih enzima prema supstratima s različitim brojem skupina podložnih fosforilaciji, odnosno prema polipeptidnome polimeru glutaminske kiseline i tirozina Poly Glu:Tyr (4:1) i M3-01 peptidu. Razvoj učinkovitih kinaznih inhibitora važan je ne samo za prevenciju i liječenje mnogih bolesti već i za bolje razumijevanje uloge proteinskih kinaza u organizmu.
 
Publisher Croatian Chemical Society
 
Date 2005-09-15
 
Type text
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
 
Format application/pdf
 
Identifier http://hrcak.srce.hr/44
http://hrcak.srce.hr/file/44
 
Source Croatica Chemica Acta; Vol.78 No.3; ISSN 0011-1643 (Print); ISSN 1334-417X (Online)
 
Language en
 
Rights info:eu-repo/semantics/openAccess
Parts of the contents of Croat. Chem. Acta (e. g. figures or tables) may be reproduced without prior permission, provided reference is made to their source.