{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:41:58Z","timestamp":1791175318899,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,3,1]]},"abstract":"<jats:p>Previous work from our laboratory has demonstrated that the Ca2+\u2014calmodulin complex inhibits the intrinsic tyrosine kinase activity of the epidermal growth factor receptor (EGFR), and that the receptor can be isolated by Ca2+-dependent calmodulin-affinity chromatography [San Jos\u00e9, Bengur\u00eda, Geller and Villalobo (1992) J. Biol. Chem. 267, 15237\u201315245]. Moreover, we have demonstrated that the cytosolic juxtamembrane region of the human receptor (residues 645\u2013660) binds calmodulin in a Ca2+-dependent manner when this segment forms part of a recombinant fusion protein [Mart\u00edn-Nieto and Villalobo (1998) Biochemistry 37, 227\u2013236]. However, demonstration of the direct interaction between calmodulin and the whole receptor has remained elusive. In this work, we show that calmodulin, in the presence of Ca2+, forms part of a high-molecular-mass complex built upon covalent cross-linkage of the human EGFR immunoprecipitated from two cell lines overexpressing this receptor. Although several calmodulin-binding proteins co-immunoprecipitated with the EGFR, suggesting that they interact with the receptor, we demonstrated using overlay techniques that biotinylated calmodulin binds directly to the receptor in a Ca2+-dependent manner without the mediation of any adaptor calmodulin-binding protein. Calmodulin binds to the EGFR with an apparent dissociation constant (K\u2032d) of approx. 0.2\u20130.3\u03bcM. Treatment of cells with epidermal growth factor, or with inhibitors of protein kinase C and calmodulin-dependent protein kinase II, or treatment of the immunoprecipitated receptor with alkaline phosphatase, does not significantly affect the binding of biotinylated calmodulin to the receptor.<\/jats:p>","DOI":"10.1042\/bj3620499","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T22:18:36Z","timestamp":1439245116000},"page":"499-505","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Evidence for the direct interaction between calmodulin and the human epidermal growth factor receptor"],"prefix":"10.1042","volume":"362","author":[{"given":"Hongbing","family":"LI","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas, Consejo Superior de Investigaciones Cient\u00edficas and Universidad Aut\u00f3noma de Madrid, c\/Arturo Duperier 4, E-28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"VILLALOBO","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas, Consejo Superior de Investigaciones Cient\u00edficas and Universidad Aut\u00f3noma de Madrid, c\/Arturo Duperier 4, E-28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2002,2,22]]},"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/362\/2\/499\/709100\/bj3620499.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/362\/2\/499\/709100\/bj3620499.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T12:05:17Z","timestamp":1637582717000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/362\/2\/499\/39983\/Evidence-for-the-direct-interaction-between"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,2,22]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,3,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3620499","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,2,22]]}}}