{ "indexed": { "date-parts": [ [ 2020, 5, 5 ] ], "date-time": "2020-05-05T11:24:12Z", "timestamp": 1588677852676 }, "reference-count": 59, "publisher": "eLife Sciences Publications, Ltd", "license": [ { "URL": "http:\/\/creativecommons.org\/licenses\/by\/3.0\/", "start": { "date-parts": [ [ 2014, 3, 18 ] ], "date-time": "2014-03-18T00:00:00Z", "timestamp": 1395100800000 }, "delay-in-days": 0, "content-version": "vor" }, { "URL": "http:\/\/creativecommons.org\/licenses\/by\/3.0\/", "start": { "date-parts": [ [ 2014, 3, 18 ] ], "date-time": "2014-03-18T00:00:00Z", "timestamp": 1395100800000 }, "delay-in-days": 0, "content-version": "am" }, { "URL": "http:\/\/creativecommons.org\/licenses\/by\/3.0\/", "start": { "date-parts": [ [ 2014, 3, 18 ] ], "date-time": "2014-03-18T00:00:00Z", "timestamp": 1395100800000 }, "delay-in-days": 0, "content-version": "tdm" }, { "URL": "http:\/\/creativecommons.org\/licenses\/by\/3.0\/", "start": { "date-parts": [ [ 2014, 3, 18 ] ], "date-time": "2014-03-18T00:00:00Z", "timestamp": 1395100800000 }, "delay-in-days": 0, "content-version": "vor" }, { "URL": "http:\/\/creativecommons.org\/licenses\/by\/3.0\/", "start": { "date-parts": [ [ 2014, 3, 18 ] ], "date-time": "2014-03-18T00:00:00Z", "timestamp": 1395100800000 }, "delay-in-days": 0, "content-version": "am" }, { "URL": "http:\/\/creativecommons.org\/licenses\/by\/3.0\/", "start": { "date-parts": [ [ 2014, 3, 18 ] ], "date-time": "2014-03-18T00:00:00Z", "timestamp": 1395100800000 }, "delay-in-days": 0, "content-version": "tdm" } ], "funder": [ { "DOI": "10.13039\/100000002", "name": "National Institutes of Health", "doi-asserted-by": "crossref", "award": [ "GM56169", "AG39420", "T32 GM007276" ] }, { "DOI": "10.13039\/100000968", "name": "American Heart Association", "doi-asserted-by": "crossref", "award": [ "Postdoctoral Fellowship" ] }, { "DOI": "10.13039\/501100000024", "name": "Canadian Institutes of Health Research", "doi-asserted-by": "crossref", "award": [ "Postdoctoral Fellowship" ] }, { "DOI": "10.13039\/100000002", "name": "National Institutes of Health", "doi-asserted-by": "publisher", "award": [ "GM56169", "AG39420", "T32 GM007276" ] }, { "DOI": "10.13039\/100000968", "name": "American Heart Association", "doi-asserted-by": "publisher", "award": [ "Postdoctoral Fellowship" ] }, { "DOI": "10.13039\/501100000024", "name": "Canadian Institutes of Health Research", "doi-asserted-by": "publisher", "award": [ "Postdoctoral Fellowship" ] } ], "content-domain": { "domain": [ "www.elifesciences.org" ], "crossmark-restriction": false }, "short-container-title": [], "abstract": "Glycogen synthase kinase-3 (GSK-3) is a key regulator of many cellular signaling pathways. Unlike most kinases, GSK-3 is controlled by inhibition rather than by specific activation. In the insulin and several other signaling pathways, phosphorylation of a serine present in a conserved sequence near the amino terminus of GSK-3 generates an auto-inhibitory peptide. In contrast, Wnt\/\u03b2-catenin signal transduction requires phosphorylation of Ser\/Pro rich sequences present in the Wnt co-receptors LRP5\/6, and these motifs inhibit GSK-3 activity. We present crystal structures of GSK-3 bound to its phosphorylated N-terminus and to two of the phosphorylated LRP6 motifs. A conserved loop unique to GSK-3 undergoes a dramatic conformational change that clamps the bound pseudo-substrate peptides, and reveals the mechanism of primed substrate recognition. The structures rationalize target sequence preferences and suggest avenues for the design of inhibitors selective for a subset of pathways regulated by GSK-3.<\/jats:p>", "DOI": "10.7554\/elife.01998", "type": "journal-article", "created": { "date-parts": [ [ 2014, 3, 18 ] ], "date-time": "2014-03-18T15:23:32Z", "timestamp": 1395156212000 }, "source": "Crossref", "is-referenced-by-count": 56, "title": [ "Structural basis of GSK-3 inhibition by N-terminal phosphorylation and by the Wnt receptor LRP6" ], "prefix": "10.7554", "volume": "3", "author": [ { "given": "Jennifer L", "family": "Stamos", "sequence": "first", "affiliation": [ { "name": "Department of Structural Biology, Stanford University, Stanford, United States" }, { "name": "Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States" } ] }, { "given": "Matthew Ling-Hon", "family": "Chu", "sequence": "additional", "affiliation": [ { "name": "Department of Structural Biology, Stanford University, Stanford, United States" }, { "name": "Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States" } ] }, { "given": "Michael D", "family": "Enos", "sequence": "additional", "affiliation": [ { "name": "Department of Structural Biology, Stanford University, Stanford, United States" }, { "name": "Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States" } ] }, { "given": "Niket", "family": "Shah", "sequence": "additional", "affiliation": [ { "name": "Department of Structural Biology, Stanford University, Stanford, United States" }, { "name": "Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States" } ] }, { "given": "William I", "family": "Weis", "sequence": "additional", "affiliation": [ { "name": "Department of Structural Biology, Stanford University, Stanford, United States" }, { "name": "Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States" } ] } ], "member": "4374", "published-online": { "date-parts": [ [ 2014, 3, 18 ] ] }, "reference": [ { "key": "bib1", "doi-asserted-by": "publisher", "first-page": "213", "DOI": "10.1107\/S0907444909052925", "article-title": "PHENIX: a comprehensive Python-based system for macromolecular structure solution", "volume": "66", "author": "Adams", "year": "2010", "journal-title": "Acta Crystallographica Section D Biological Crystallography" }, { "key": "bib2", "doi-asserted-by": "publisher", "first-page": "2527", "DOI": "10.1021\/cr000110o", "article-title": "Glycogen synthase kinase-3: properties, functions, and regulation", "volume": "101", "author": "Ali", "year": "2001", "journal-title": "Chemical Reviews" }, { "key": "bib3", "doi-asserted-by": "publisher", "first-page": "2264", "DOI": "10.2174\/138161211797052484", "article-title": "The possible involvement of glycogen synthase kinase-3 (GSK-3) in diabetes, cancer and central nervous system diseases", "volume": 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