{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:46:08Z","timestamp":1791978368344,"version":"4.4.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,3,15]]},"abstract":"<jats:p>By mediating the coupled movement of Na, K, and Cl ions across the plasma membrane of most animal cells, the bumetanide-sensitive Na-K-Cl cotransporter (NKCC) plays a vital role in the regulation of ionic balance and cell volume. The transporter is a central element in the process of vectorial salt transport in secretory and absorptive epithelia. A cDNA encoding a Na-K-Cl cotransport protein was isolated from a shark rectal gland library by screening with monoclonal antibodies to the native shark cotransporter. The 1191-residue protein predicted from the cDNA sequence has 12 putative transmembrane domains flanked by large cytoplasmic N and C termini. Regulatory phosphoacceptor residues in isolated peptides are identified as Thr-189 and Thr-1114 in the predicted sequence. Northern blot analysis identified a 7.4-kb mRNA in rectal gland and most other shark tissues; a 5.2-kb mRNA was restricted to shark kidney. Homology with an uncharacterized gene from Caenorhabditis elegans and with the thiazide-sensitive Na-Cl cotransporter of flounder urinary bladder was found over most of the coding region; shorter stretches of homology were found with a C. elegans cDNA and with an uncharacterized gene of cyanobacterium. Human HEK-293 cells have been stably transfected with the shark cDNA and shown to express Na-K-Cl cotransport activity with the bumetanide sensitivity of the shark protein. The expressed transporter is functionally quiescent in the host cells and can be activated by depleting the cells of chloride.<\/jats:p>","DOI":"10.1073\/pnas.91.6.2201","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:05:57Z","timestamp":1149066357000},"page":"2201-2205","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":350,"title":["Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter."],"prefix":"10.1073","volume":"91","author":[{"given":"J C","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Lytle","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T T","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"E","family":"Benz","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"3rd","given":"B","family":"Forbush","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,3,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.6.2201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:49:53Z","timestamp":1649857793000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.6.2201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3,15]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1994,3,15]]}},"alternative-id":["10.1073\/pnas.91.6.2201"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.6.2201","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,3,15]]},"assertion":[{"value":"1994-03-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}