title: Kinetic responses of β-catenin specify the sites of Wnt control.
abstract: Despite more than 30 years of work on the Wnt signaling pathway, the basic mechanism of how the extracellular Wnt signal increases the intracellular concentration of β-catenin is still contentious. Circumventing much of the detailed biochemistry, we used basic principles of chemical kinetics coupled with quantitative measurements to define the reactions on β-catenin directly affected by the Wnt signal. We conclude that the core signal transduction mechanism is relatively simple, with only two regulated phosphorylation steps. Their partial inhibition gives rise to the full dynamics of the response and subsequently maintains a steady state in which the concentration of β-catenin is increased.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Hernández
authors.forename: Allon M
authors.initials: AM
authors.lastname: Klein
authors.forename: Marc W
authors.initials: MW
authors.lastname: Kirschner
mesh_terms: D047389:Casein Kinase I / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D010766:Phosphorylation; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D060509:Wnt3A Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D051153:Wnt Proteins; D060509:Wnt3A Protein; D051176:beta Catenin; D047389:Casein Kinase I; D038362:Glycogen Synthase Kinase 3; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde