Genetic selection for modulators of the MAP kinase and beta-catenin growth-control pathways in mammalian cells.
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.
Wheatley
William
W
Arcaris, Inc., 615 Arapeen Drive, Salt Lake City, Utah 84108, USA.
Yoo
Sanghee
S
Pierce
Michael
M
Rebentisch
Matthew
M
Endo
Mark
M
Peterson
Isaac
I
Stump
Mark
M
McCormack
Ken
K
Garcia-Guzman
Miguel
M
Kamb
Alexander
A
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
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D020928:Mitogen-Activated Protein Kinases