Kinetic Responses of β-Catenin Specify the Sites of Wnt Control
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...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2012-12, Vol.338 (6112), p.1337-1340 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Hernández, Ana R. Klein, Allon M. Kirschner, Marc W. |
| description | 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. |
| doi_str_mv | 10.1126/science.1228734 |
| format | Article |
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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.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>beta Catenin - metabolism</subject><subject>Biochemical mechanisms</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Casein Kinase I - chemistry</subject><subject>Casein Kinase I - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Control systems</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Enzymes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Leupeptins - pharmacology</subject><subject>Material degradation</subject><subject>Mental stimulation</subject><subject>Molecular and cellular biology</subject><subject>Online</subject><subject>Pathways</subject><subject>Phosphatases</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Quantitative analysis</subject><subject>Reaction kinetics</subject><subject>Receptors</subject><subject>Signal Transduction</subject><subject>Signalling systems</subject><subject>Wnt Proteins - metabolism</subject><subject>Wnt3A Protein - metabolism</subject><subject>Written correspondence</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkL1OwzAURi0EoqUwM4GyILEEfH2b2N5AFX8CCYmCGCPHvRFGqVNid-hr8SA8E0ENPxvTHb5zz3AY2wd-AiDy02AdeUsnIISSON5gQ-A6S7XguMmGnGOeKi6zAdsJ4ZXzbtO4zQYCAZWWasjObp2n6GzyQGHR-EAhaark4z2dmEje-WS6IOuqVRJfKJm6uN6ffUwmjY9tU--yrcrUgfb6O2JPlxePk-v07v7qZnJ-l1pUIqaVyWTFy1zlEksqNc1m1qCyBFKXGRqTQ6ZBSgBdCckNZpaI40yPscy1IByx47V30TZvSwqxmLtgqa6Np2YZClBcdUUEZP-jAmUGXCrRoadr1LZNCC1VxaJ1c9OuCuDFV-GiL1z0hbuPw16-LOc0--G_k3bAUQ-YYE1dtcZbF365XGrgnWrEDtbca4hN-8eDKDiM8RPdu42k</recordid><startdate>20121207</startdate><enddate>20121207</enddate><creator>Hernández, Ana R.</creator><creator>Klein, Allon M.</creator><creator>Kirschner, Marc W.</creator><general>American Association for the Advancement of Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope></search><sort><creationdate>20121207</creationdate><title>Kinetic Responses of β-Catenin Specify the Sites of Wnt Control</title><author>Hernández, Ana R. ; Klein, Allon M. ; Kirschner, Marc W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-fa57f0b68673beb9eddca38ce179b53aa6159177119f270a35cee03d943b692e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>beta Catenin - metabolism</topic><topic>Biochemical mechanisms</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Casein Kinase I - chemistry</topic><topic>Casein Kinase I - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Control systems</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Enzymes</topic><topic>Fundamental and applied biological sciences. 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| ispartof | Science (American Association for the Advancement of Science), 2012-12, Vol.338 (6112), p.1337-1340 |
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| source | MEDLINE; Science Magazine; JSTOR Archive Collection A-Z Listing |
| subjects | Analytical, structural and metabolic biochemistry beta Catenin - metabolism Biochemical mechanisms Biochemistry Biological and medical sciences Cancer Casein Kinase I - chemistry Casein Kinase I - metabolism Cell Line, Tumor Control systems Cysteine Proteinase Inhibitors - pharmacology Enzymes Fundamental and applied biological sciences. Psychology Glycogen Synthase Kinase 3 - metabolism HEK293 Cells Humans Kinetics Leupeptins - pharmacology Material degradation Mental stimulation Molecular and cellular biology Online Pathways Phosphatases Phosphorylation Proteins Quantitative analysis Reaction kinetics Receptors Signal Transduction Signalling systems Wnt Proteins - metabolism Wnt3A Protein - metabolism Written correspondence |
| title | Kinetic Responses of β-Catenin Specify the Sites of Wnt Control |
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