{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:18:09Z","timestamp":1780546689640,"version":"3.54.1"},"reference-count":67,"publisher":"The Company of Biologists","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,1]]},"abstract":"<jats:p>Mitogen-inducible gene 6 [Mig-6; Errfi1 (ErbB receptor feedback inhibitor 1); RALT (receptor-associated late transducer); gene 33] is a ubiquitously expressed adaptor protein containing CRIB,SH3 and 14-3-3 interacting domains and has been shown to negatively regulate EGF signaling. Ablation of Mig-6 results in a partial lethal phenotype in which surviving mice acquire degenerative joint diseases and tumors in multiple organs. We have determined that the early lethality in Mig-6-\/- mice occurs in the perinatal period, with mice displaying abnormal lung development. Histological examination of Mig-6-\/- lungs (E15.5-P3) revealed reduced septation,airway over-branching, alveolar type II cell hyperplasia, and disturbed vascular formation. In neonatal Mig-6-\/- lungs, cell proliferation increased in the airway epithelium but apoptosis increased in the blood vessels. Adult Mig-6-\/- mice developed features of chronic obstructive pulmonary disease (COPD); however, when Mig-6was inducibly ablated in adult mice (Mig-6d\/d), the lungs were normal. Knockdown of MIG-6 in H441 human bronchiolar epithelial cells increased phospho-EGFR and phospho-AKT levels as well as cell proliferation, whereas knockdown of MIG-6 in human lung microvascular endothelial (HMVEC-L) cells promoted their apoptosis. These results demonstrate that Mig-6 is required for prenatal and perinatal lung development, in part through the regulation of EGF signaling, as well as for maintaining proper pulmonary vascularization.<\/jats:p>","DOI":"10.1242\/dev.032979","type":"journal-article","created":{"date-parts":[[2009,8,27]],"date-time":"2009-08-27T00:53:38Z","timestamp":1251334418000},"page":"3347-3356","source":"Crossref","is-referenced-by-count":40,"title":["<i>Mig-6<\/i>is required for appropriate lung development and to ensure normal adult lung homeostasis"],"prefix":"10.1242","volume":"136","author":[{"given":"Nili","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine,Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Nam","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine,Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Gabriela","family":"Raso","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, University of Texas,M.D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Wistuba","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, University of Texas,M.D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute of Immunology, NUI Maynooth, Co. Kildare, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, University of Texas,M.D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Kurie","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, University of Texas,M.D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, University of Texas,M.D. Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas M.D Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Columbia University Health Science Division,Columbia University, New York, NY 10027, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Wook","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine,Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco J.","family":"DeMayo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine,Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042621392508000_REF1","doi-asserted-by":"crossref","unstructured":"Amatschek, S., Koenig, U., Auer, H., Steinlein, P., Pacher, M.,Gruenfelder, A., Dekan, G., Vogl, S., Kubista, E., Heider, K. 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