{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:32:14Z","timestamp":1790973134562,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2005,8,1]],"date-time":"2005-08-01T00:00:00Z","timestamp":1122854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The molecular mechanisms of airway smooth muscle hypertrophy, a feature of severe asthma, are poorly understood. We previously established a conditionally immortalized human bronchial smooth muscle cell line with a temperature-sensitive SV40 large T antigen. Temperature shift and loss of large T cause G1-phase cell cycle arrest that is accompanied by increased airway smooth muscle cell size. In the present study, we hypothesized that phosphorylation of eukaryotic initiation factor-4E (eIF4E)-binding protein (4E-BP), which subsequently releases eIF4E and initiates cap-dependent mRNA translation, was required for airway smooth muscle hypertrophy. Treatment of cells with chemical inhibitors of PI 3-kinase and mammalian target of rapamycin blocked protein synthesis and cell growth while decreasing the phosphorylation of 4E-BP and increasing the binding of 4E-BP to eIF4E, consistent with the notion that 4E-BP1 phosphorylation and eIF4E function are required for hypertrophy. To test this directly, we infected cells with a retrovirus encoding a phosphorylation site mutant of 4E-BP1 (AA-4E-BP-1) that dominantly inhibits eIF4E. Upon temperature shift, cells infected with AA-4E-BP-1, but not empty vector, failed to undergo hypertrophic growth. We conclude that phosphorylation of 4E-BP, eIF4E release, and cap-dependent protein synthesis are required for hypertrophy of human airway smooth muscle cells.<\/jats:p>","DOI":"10.1165\/rcmb.2004-0411oc","type":"journal-article","created":{"date-parts":[[2005,5,18]],"date-time":"2005-05-18T20:33:53Z","timestamp":1116448433000},"page":"195-202","source":"Crossref","is-referenced-by-count":54,"title":["4E-Binding Protein Phosphorylation and Eukaryotic Initiation Factor-4E Release Are Required for Airway Smooth Muscle Hypertrophy"],"prefix":"10.1093","volume":"33","author":[{"given":"Limei","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases and Department of Molecular and Integrative Physiology, and Department of Cell and Developmental Biology and Department of Medicine, University of Michigan, Ann Arbor, Michigan; and Department of Pediatrics, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases and Department of Molecular and Integrative Physiology, and Department of Cell and Developmental Biology and Department of Medicine, University of Michigan, Ann Arbor, Michigan; and Department of Pediatrics, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Kelley","family":"Bentley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases and Department of Molecular and Integrative Physiology, and Department of Cell and Developmental Biology and Department of Medicine, University of Michigan, Ann Arbor, Michigan; and Department of Pediatrics, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases and Department of Molecular and Integrative Physiology, and Department of Cell and Developmental Biology and Department of Medicine, University of Michigan, Ann Arbor, Michigan; and Department of Pediatrics, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable 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