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  • Title: Functional overlap and regulatory links shape genetic interactions between signaling pathways.
    Author: van Wageningen S, Kemmeren P, Lijnzaad P, Margaritis T, Benschop JJ, de Castro IJ, van Leenen D, Groot Koerkamp MJ, Ko CW, Miles AJ, Brabers N, Brok MO, Lenstra TL, Fiedler D, Fokkens L, Aldecoa R, Apweiler E, Taliadouros V, Sameith K, van de Pasch LA, van Hooff SR, Bakker LV, Krogan NJ, Snel B, Holstege FC.
    Journal: Cell; 2010 Dec 10; 143(6):991-1004. PubMed ID: 21145464.
    Abstract:
    To understand relationships between phosphorylation-based signaling pathways, we analyzed 150 deletion mutants of protein kinases and phosphatases in S. cerevisiae using DNA microarrays. Downstream changes in gene expression were treated as a phenotypic readout. Double mutants with synthetic genetic interactions were included to investigate genetic buffering relationships such as redundancy. Three types of genetic buffering relationships are identified: mixed epistasis, complete redundancy, and quantitative redundancy. In mixed epistasis, the most common buffering relationship, different gene sets respond in different epistatic ways. Mixed epistasis arises from pairs of regulators that have only partial overlap in function and that are coupled by additional regulatory links such as repression of one by the other. Such regulatory modules confer the ability to control different combinations of processes depending on condition or context. These properties likely contribute to the evolutionary maintenance of paralogs and indicate a way in which signaling pathways connect for multiprocess control.
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