{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:15:28Z","timestamp":1791177328421,"version":"4.1.0"},"reference-count":19,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5641","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,9,26]]},"abstract":"<jats:p>Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the \u201coutput\u201d domain of N-WASP was recombined with heterologous autoinhibitory \u201cinput\u201d domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits.<\/jats:p>","DOI":"10.1126\/science.1085945","type":"journal-article","created":{"date-parts":[[2003,9,25]],"date-time":"2003-09-25T18:06:52Z","timestamp":1064513212000},"page":"1904-1908","source":"Crossref","is-referenced-by-count":266,"title":["Reprogramming Control of an Allosteric Signaling Switch Through Modular Recombination"],"prefix":"10.1126","volume":"301","author":[{"given":"John E.","family":"Dueber","sequence":"first","affiliation":[{"name":"Program in Biological Sciences, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143\u20132240, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Program in Biological Sciences, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143\u20132240, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayam","family":"Chak","sequence":"additional","affiliation":[{"name":"Program in Biological Sciences, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143\u20132240, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendell A.","family":"Lim","sequence":"additional","affiliation":[{"name":"Program in Biological Sciences, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94143\u20132240, USA."},{"name":"Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143\u20132240, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1101\/gad.14.9.1027","volume":"14","year":"2000","unstructured":"T. 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Nash, Genes Dev.14, 1027 (2000).","journal-title":"Genes Dev."},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083653"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35057062"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(02)00290-7"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.18.031502.133614"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)00061-7"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.649"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35004513"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5492.801"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.6.1299"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80732-1"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)25445-1"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00603-0"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.7.1253"},{"key":"e_1_3_1_16_2","first-page":"re8","volume":"2003","year":"2003","unstructured":"A. Zarrinpar, R. P. Bhattacharyya, W. A. Lim, Sci. STKE2003, re8 (2003).","journal-title":"Sci. STKE"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0157215"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00301-4"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(63)80091-1"},{"key":"e_1_3_1_20_2","unstructured":"We thank R. Bhattacharyya H. Bourne C. Co S. Collins E. Cunningham H. Madhani D. Mullins E. O'Shea K. Shokat J. Weissman K. Prehoda and members of the Lim laboratory for comments and discussion; and J. Taunton for Xenopus oocyte extract. Supported by grants from the Sandler Foundation NSFBio-Qubic Program the Packard Foundation and the NIH (W.A.L.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1085945","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T20:58:20Z","timestamp":1704833900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1085945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,26]]},"references-count":19,"journal-issue":{"issue":"5641","published-print":{"date-parts":[[2003,9,26]]}},"alternative-id":["10.1126\/science.1085945"],"URL":"https:\/\/doi.org\/10.1126\/science.1085945","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1015775.200168","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1015775.200896","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1015775.198313","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1015775.198705","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9,26]]}}}