{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:06:23Z","timestamp":1791162383585,"version":"4.1.0"},"reference-count":56,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,1,29]]},"abstract":"<jats:p>We have discovered that fibrillin-1, which forms extracellular microfibrils, can regulate the bioavailability of transforming growth factor (TGF) \u03b21, a powerful cytokine that modulates cell survival and phenotype. Altered TGF\u03b2 signaling is a major contributor to the pathology of Marfan syndrome (MFS) and related diseases. In the presence of cell layer extracellular matrix, a fibrillin-1 sequence encoded by exons 44\u201349 releases endogenous TGF\u03b21, thereby stimulating TGF\u03b2 receptor\u2013mediated Smad2 signaling. This altered TGF\u03b21 bioavailability does not require intact cells, proteolysis, or the altered expression of TGF\u03b21 or its receptors. Mass spectrometry revealed that a fibrillin-1 fragment containing the TGF\u03b21-releasing sequence specifically associates with full-length fibrillin-1 in cell layers. Solid-phase and BIAcore binding studies showed that this fragment interacts strongly and specifically with N-terminal fibrillin-1, thereby inhibiting the association of C-terminal latent TGF\u03b2-binding protein 1 (a component of the large latent complex [LLC]) with N-terminal fibrillin-1. By releasing LLC from microfibrils, the fibrillin-1 sequence encoded by exons 44\u201349 can contribute to MFS and related diseases.<\/jats:p>","DOI":"10.1083\/jcb.200608167","type":"journal-article","created":{"date-parts":[[2007,1,23]],"date-time":"2007-01-23T01:48:30Z","timestamp":1169516910000},"page":"355-367","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":300,"title":["Fibrillin-1 regulates the bioavailability of TGF\u03b21"],"prefix":"10.1083","volume":"176","author":[{"given":"Shazia S.","family":"Chaudhry","sequence":"first","affiliation":[{"name":"1Wellcome Trust Centre for Cell-Matrix Research"},{"name":"2UK Centre for Tissue Engineering, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart A.","family":"Cain","sequence":"additional","affiliation":[{"name":"1Wellcome Trust Centre for Cell-Matrix Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Morgan","sequence":"additional","affiliation":[{"name":"1Wellcome Trust Centre for Cell-Matrix Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Dallas","sequence":"additional","affiliation":[{"name":"3Department of Oral Biology, School of Dentistry, University of Missouri, Kansas City, MO 64108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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