title: De novo motif for kinase mediated signaling across the cell membrane.
abstract: The binding of a ligand to a cell-surface receptor represents a first step in transmitting extracellular information to the cell in order to activate downstream intracellular signaling events. This report describes the de novo engineering of cells with a transmembrane signal transduction motif that is developed from first principles. The signaling event is initiated with a polyvalent ligand that clusters an engineered receptor in the membrane. The receptor presents a cytosolic kinase substrate that undergoes autocatalytic phosphorylation when organized in a cluster, but not in the unclustered arrangement. The example described here may represent a motif that can be used in synthetic biology for the engineering of cells with novel circuits.
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Rafe T
authors.initials: RT
authors.lastname: Petty
authors.forename: Milan
authors.initials: M
authors.lastname: Mrksich
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003600:Cytosol / Q000201:enzymology; D019281:Dimerization; D005434:Flow Cytometry / Q000379:methods; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D008024:Ligands; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008024:Ligands; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl