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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,11,17]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The kinase MEKK3 (MAP3K) regulates cellular functions from proliferation to maintenance of cell identity, and plays an important role in cardiovascular development, yet little is known about how it is regulated. Loss-of-function mutations in\n                    <jats:italic>CCM1<\/jats:italic>\n                    ,\n                    <jats:italic>CCM2<\/jats:italic>\n                    , or\n                    <jats:italic>CCM3<\/jats:italic>\n                    cause cerebral cavernous malformations characterized by dilated, leaky blood vessels. CCM proteins form a complex and regulate the signal strength of several pathways. We demonstrate that CCM2 and CCM2-like (CCM2L), a recently described paralog, strongly prevented the activation of MEKK3 in vitro. In zebrafish,\n                    <jats:italic>ccm2<\/jats:italic>\n                    and\n                    <jats:italic>ccm2l<\/jats:italic>\n                    genetically interacted to control cardiovascular development and body axis patterning during embryogenesis, and these were regulated by MEKK3. Therefore, two homologous CCM proteins regulate MEKK3 activity, and thus may modulate the strength of key signaling pathways.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1510495112","type":"journal-article","created":{"date-parts":[[2015,11,4]],"date-time":"2015-11-04T23:09:10Z","timestamp":1446678550000},"page":"14284-14289","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["The cerebral cavernous malformation proteins CCM2L and CCM2 prevent the activation of the MAP kinase MEKK3"],"prefix":"10.1073","volume":"112","author":[{"given":"Xavier","family":"Cullere","sequence":"first","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Plovie","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calum A.","family":"MacRae","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya N.","family":"Mayadas","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,11,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.02.004"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1532-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39679"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.12.006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2012-0243"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3171\/2010.5.FOCUS1090"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000132107"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12207"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.12.016"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.06.004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.01.006"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1071"},{"key":"e_1_3_3_13_2","first-page":"37","article-title":"MEK5\/ERK5 pathway: The first fifteen years","volume":"1825","author":"Drew BA","year":"2012","unstructured":"BA Drew, ME Burow, BS Beckman, MEK5\/ERK5 pathway: The first fifteen years. 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