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Genetic Selection for Modulators of the MAP Kinase and β-Catenin Growth-Control Pathways in Mammalian Cells

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Abstract

Transdominant genetic selections can yield protein fragment and peptide modulators of specific biochemical pathways. In yeast, such screens have been highly successful in targeting the MAP (mitogen-activated protein) kinase growth-control pathway. We performed a similar type of selection aimed at recovery of modulators of the mammalian MAP kinase cascade. Two pathway activators were identified, fragments of the TrkB and Raf-1 kinases. In a second selection directed at the β-catenin growth-control pathway, three different clones encoding cadherin fragments were recovered. In neither selection were peptide inhibitors observed. We conclude that some transdominant selections in mammalian cells can readily yield high-penetrance protein fragments, but may be less amenable to isolation of peptide inhibitors.

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Wheatley, W., Yoo, S., Pierce, M. et al. Genetic Selection for Modulators of the MAP Kinase and β-Catenin Growth-Control Pathways in Mammalian Cells. Biochem Genet 40, 359–378 (2002). https://doi.org/10.1023/A:1020705210855

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