{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:03:52Z","timestamp":1770980632131,"version":"3.50.1"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,3,1]]},"abstract":"<jats:p>We demonstrate that a Hirschsprung (HSCR) mutation in the tyrosine kinase domain of the RET proto-oncogene abolishes in cis the tyrosine-phosphorylation associated with the activating mutation in multiple endocrine neoplasia type 2A (MEN2A) in transiently transfected Cos cells. Yet the double mutant RET2AHS retains the ability to form stable dimers, thus dissociating the dimerization from the phosphorylation potential. Co-transfection experiments with single and double mutants carrying plasmids RET2A and RET2AHS in different ratios drastically reduced the phosphorylation levels of the RET2A protein, suggesting a dominant-negative effect of the HSCR mutation. Also, the phosphorylation associated with the multiple endocrine neoplasia type 2B (MEN2B) allele was affected in experiments with single and double mutants carrying plasmids co-transfected under the same conditions. Finally, analysis of the enzymic activity of MEN2A and MEN2B tumours confirmed the relative levels of tyrosine phosphorylation observed in Cos cells, indicating that this condition, in vivo, may account for the RET transforming potential.<\/jats:p>","DOI":"10.1042\/bj3140397","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:47:57Z","timestamp":1439243277000},"page":"397-400","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A mutation in the <i>RET<\/i> proto-oncogene in Hirschsprung's disease affects the tyrosine kinase activity associated with multiple endocrine neoplasia type 2A and 2B"],"prefix":"10.1042","volume":"314","author":[{"given":"Maria Pia","family":"COSMA","sequence":"first","affiliation":[{"name":"Dipartimento di Biochimica e Biotecnologie Mediche, CEINGE, Centro di Ingegneria Genetica"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"PANARIELLO","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica e Biotecnologie Mediche, CEINGE, Centro di Ingegneria Genetica"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"QUADRO","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica e Biotecnologie Mediche, CEINGE, Centro di Ingegneria Genetica"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina A.","family":"DATHAN","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia e Patologia Cellulare e Molecolare, Centro di Endocrinologia e Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 degli Studi di Napoli \u2018Federico II\u2019, Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olimpia","family":"FATTORUSO","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica e Biotecnologie Mediche, CEINGE, Centro di Ingegneria Genetica"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"COLANTUONI","sequence":"additional","affiliation":[{"name":"Dipartimento di Biochimica e Biotecnologie Mediche, CEINGE, Centro di Ingegneria Genetica"},{"name":"Facolt\u00e0 di Farmacia, Universit\u00e0 di Reggio Calabria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/314\/2\/397\/619061\/bj3140397.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/314\/2\/397\/619061\/bj3140397.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T23:46:03Z","timestamp":1637711163000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/314\/2\/397\/32093\/A-mutation-in-the-RET-proto-oncogene-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,3,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1996,3,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3140397","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,3,1]]}}}