{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T01:49:18Z","timestamp":1768096158841,"version":"3.49.0"},"reference-count":52,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,5,15]]},"abstract":"<jats:p>AS (Apert syndrome) is a congenital disease composed of skeletal, visceral and neural abnormalities, caused by dominant-acting mutations in FGFR2 [FGF (fibroblast growth factor) receptor 2]. Multiple FGFR2 splice variants are generated through alternative splicing, including PTC (premature termination codon)-containing transcripts that are normally eliminated via the NMD (nonsense-mediated decay) pathway. We have discovered that a soluble truncated FGFR2 molecule encoded by a PTC-containing transcript is up-regulated and persists in tissues of an AS mouse model. We have termed this IIIa\u2013TM as it arises from aberrant splicing of FGFR2 exon 7 (IIIa) into exon 10 [TM (transmembrane domain)]. IIIa\u2013TM is glycosylated and can modulate the binding of FGF1 to FGFR2 molecules in BIAcore-binding assays. We also show that IIIa\u2013TM can negatively regulate FGF signalling in vitro and in vivo. AS phenotypes are thought to result from gain-of-FGFR2 signalling, but our findings suggest that IIIa\u2013TM can contribute to these through a loss-of-FGFR2 function mechanism. Moreover, our findings raise the interesting possibility that FGFR2 signalling may be a regulator of the NMD pathway.<\/jats:p>","DOI":"10.1042\/bj20100884","type":"journal-article","created":{"date-parts":[[2011,3,4]],"date-time":"2011-03-04T09:26:42Z","timestamp":1299230802000},"page":"71-81","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Identification and characterization of an inhibitory fibroblast growth factor receptor 2 (FGFR2) molecule, up-regulated in an Apert Syndrome mouse model"],"prefix":"10.1042","volume":"436","author":[{"given":"Lee\u00a0M.","family":"Wheldon","sequence":"first","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naila","family":"Khodabukus","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susannah\u00a0J.","family":"Patey","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence\u00a0G.","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of East Anglia, Norwich, Norfolk NR4 7TJ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John\u00a0K.","family":"Heath","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Edgbaston B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad\u00a0K.","family":"Hajihosseini","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of East Anglia, Norwich, Norfolk NR4 7TJ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2011,4,27]]},"reference":[{"key":"2021112214445672900_B1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/5096","article-title":"Fgf10 is essential for limb and lung formation","volume":"21","author":"Sekine","year":"1999","journal-title":"Nat. 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