title: Genetic selection for modulators of the MAP kinase and beta-catenin growth-control pathways in mammalian cells.
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.
authors.affiliation: Arcaris, Inc., 615 Arapeen Drive, Salt Lake City, Utah 84108, USA.
authors.forename: William
authors.initials: W
authors.lastname: Wheatley
authors.forename: Sanghee
authors.initials: S
authors.lastname: Yoo
authors.forename: Michael
authors.initials: M
authors.lastname: Pierce
authors.forename: Matthew
authors.initials: M
authors.lastname: Rebentisch
authors.forename: Mark
authors.initials: M
authors.lastname: Endo
authors.forename: Isaac
authors.initials: I
authors.lastname: Peterson
authors.forename: Mark
authors.initials: M
authors.lastname: Stump
authors.forename: Ken
authors.initials: K
authors.lastname: McCormack
authors.forename: Miguel
authors.initials: M
authors.lastname: Garcia-Guzman
authors.forename: Alexander
authors.initials: A
authors.lastname: Kamb
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001681:Biological Assay; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000502:physiology; D012641:Selection, Genetic; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D020928:Mitogen-Activated Protein Kinases