Genetic selection for modulators of the MAP kinase and beta-catenin growth-control pathways in mammalian cells |
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Authors: | Wheatley William Yoo Sanghee Pierce Michael Rebentisch Matthew Endo Mark Peterson Isaac Stump Mark McCormack Ken Garcia-Guzman Miguel Kamb Alexander |
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Affiliation: | Arcaris, Inc., 615 Arapeen Drive, Salt Lake City, Utah 84108, USA. |
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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 beta-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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