{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:23:41Z","timestamp":1790979821398,"version":"4.1.0"},"reference-count":66,"publisher":"American Society for Cell Biology (ASCB)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p>Cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein (CFTR), a cAMP\/protein kinase A (PKA) and ATP-regulated Cl<jats:sup>\u2212<\/jats:sup>channel. CFTR is increasingly recognized as a component of multiprotein complexes and although several inhibitory proteins to CFTR have been identified, protein complexes that stimulate CFTR function remain less well characterized. We report that annexin 2 (anx 2)\u2013S100A10 forms a functional cAMP\/PKA\/calcineurin (CaN)-dependent complex with CFTR. Cell stimulation with forskolin\/3-isobutyl-1-methylxanthine significantly increases the amount of anx 2\u2013S100A10 that reciprocally coimmunoprecipitates with cell surface CFTR and calyculin A. Preinhibition with PKA or CaN inhibitors attenuates the interaction. Furthermore, we find that the acetylated peptide (STVHEILCKLSLEG, Ac1-14), but not the nonacetylated equivalent N1-14, corresponding to the S100A10 binding site on anx 2, disrupts the anx 2\u2013S100A10\/CFTR complex. Analysis of 4,4\u2032-diisothiocyanatostilbene-2,2\u2032-disulfonic acid (DIDS) and CFTR<jats:sub>inh172<\/jats:sub>-sensitive currents, taken as indication of the outwardly rectifying Cl<jats:sup>\u2212<\/jats:sup>channels (ORCC) and CFTR-mediated currents, respectively, showed that Ac1-14, but not N1-14, inhibits both the cAMP\/PKA-dependent ORCC and CFTR activities. CaN inhibitors (cypermethrin, cyclosporin A) discriminated between ORCC\/CFTR by inhibiting the CFTR<jats:sub>inh172<\/jats:sub>-, but not the DIDS-sensitive currents, by &gt;70%. Furthermore, peptide Ac1-14 inhibited acetylcholine-induced short-circuit current measured across a sheet of intact intestinal biopsy. Our data suggests that the anx 2\u2013S100A10\/CFTR complex is important for CFTR function across epithelia.<\/jats:p>","DOI":"10.1091\/mbc.e07-02-0126","type":"journal-article","created":{"date-parts":[[2007,6,21]],"date-time":"2007-06-21T01:40:37Z","timestamp":1182390037000},"page":"3388-3397","source":"Crossref","is-referenced-by-count":45,"title":["The Formation of the cAMP\/Protein Kinase A-dependent Annexin 2\u2013S100A10 Complex with Cystic Fibrosis Conductance Regulator Protein (CFTR) Regulates CFTR Channel Function"],"prefix":"10.1091","volume":"18","author":[{"given":"Lee A.","family":"Borthwick","sequence":"first","affiliation":[{"name":"*Academic Unit of Child Health, The University of Sheffield, Sheffield Children's Hospital, Sheffield, S10 2TH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Mcgaw","sequence":"additional","affiliation":[{"name":"*Academic Unit of Child Health, The University of Sheffield, Sheffield Children's Hospital, Sheffield, S10 2TH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Conner","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, FL 33101;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"*Academic Unit of Child Health, The University of Sheffield, Sheffield Children's Hospital, Sheffield, S10 2TH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Gerke","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry, University of M\u00fcnster, D-48149 M\u00fcnster, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Mehta","sequence":"additional","affiliation":[{"name":"Tayside Institute of Child Health, Ninewells Hospital and Medical School, University of Dundee, DD1 9SY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Robson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, The University of Sheffield, Sheffield, S10 2TN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richmond","family":"Muimo","sequence":"additional","affiliation":[{"name":"*Academic Unit of Child Health, The University of Sheffield, Sheffield Children's Hospital, Sheffield, S10 2TH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/340313a0","volume":"340","author":"Ali S. 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