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MAYADA SİFİNGOLİPİD İLE DİĞER SİNYAL İLETİMİ MEKANİZMALARI ARASINDAKİ ETKİLEŞİMLERİN BELİRLENMESİ

DECIPHERING THE CROSS-TALK BETWEEN SPHINGOLIPID MECHANISM AND SIGNALING PATHWAYS IN BAKER’S YEAST

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Abstract (2. Language): 
As most of the known diseases exhibit dysfunctional aspects in the signal transduction networks, there has been a great deal of enthusiasm to identify novel drug targets based on the knowledge of key signal transduction components and their links to diseases. In the present study, a computational framework was recruited for the reconstruction of protein-protein interaction networks of specific signaling mechanisms in Baker’s yeast. The objective was to analyze the interconnection between these signaling networks in order to identify the possible crosstalks between sphingolipid signaling and other signaling mechanisms. These networks are composed of the candidate proteins belonging to sphingolipid signaling, target of rapamycin (TOR) signaling, high osmolarity glycerol (HOG) signaling, pheromone response and calcium (Ca) mediated signaling in Saccharomyces cerevisiae. A detailed map including physical and functional connections that link the relevant signal transduction components to each other and to adjacent networks is developed. The proposed framework can effectively be used as a tool to give insight into the important and complicated network of signaling in higher eukaryotes.
Abstract (Original Language): 
Bilinen birçok hastalığın, sinyal ileti ağyapılarında işlev bozukluğundan kaynaklandığı bulgusuna dayanarak, anahtar sinyal ileti unsurları ve bunların hastalıklarla bağlantıları üstüne bilinenlerin baz alınması yoluyla yeni ilaç hedefleri saptanması son yıllarda çok ilgi çekmektedir. Bu çalışmada da, mayaya özgü sinyal ileti mekanizmalarının protein-protein etkileşim ağyapıları oluşturulması hesapsal bir çerçevede incelenmiştir. Amaç, mayadaki değişik sinyal ileti ağyapılarının birbirleriyle bağıntılarını inceleyerek, özellikle sifingolipid sinyal ileti mekanizması ile diğer sinyal iletimi mekanizmaları arasındaki olası etkileşimleri belirlemektir. Bu ağyapıları oluşturan aday proteinler mayadaki sifingolipid, Rapamisin hedefi (TOR), yüksek ozmolarite gliserol (HOG), feromon tepki ve kalsiyum ilintili sinyal ileti ağyapılarında görev almaktadırlar. İlgili sinyal ileti unsurlarını birbirlerine ve komşuağyapılarına birleştiren fiziksel ve işlevsel bağlantıları detaylı gösteren bir yolizi haritası hazırlanmıştır. Burada önerilen hesapsal yöntem, yüksek ökaryotlardaki önemli ve karmaşık sinyal ileti ağyapılarını incelemede de etkili olarak kullanılabilir.
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