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dc.contributor.authorZhang, J
dc.contributor.authorKarimy, JK
dc.contributor.authorDelpire, E
dc.contributor.authorKahle, KT
dc.date.accessioned2018-07-06T08:54:48Z
dc.date.issued2017-07-06
dc.description.abstractIntroduction: The mammalian SPS1-related proline/alanine-rich serine-threonine kinase SPAK (STK39) modulates ion transport across and between epithelial cells in response to environmental stimuli such osmotic stress and inflammation. Research over the last decade has established a central role for SPAK in the regulation of ion and water transport in the distal nephron, colonic crypts, and pancreatic ducts, and has implicated deregulated SPAK signaling in NaCl-sensitive hypertension, ulcerative colitis and Crohn's disease, and cystic fibrosis. Areas covered: We review recent advances in our understanding of the role of SPAK kinase in the regulation of epithelial transport. We highlight how SPAK signaling - including its upstream Cl- sensitive activators, the WNK kinases, and its downstream ion transport targets, the cation- Cl- cotransporters contribute to human disease. We discuss prospects for the pharmacotherapeutic targeting of SPAK kinase in specific human disorders that feature impaired epithelial homeostasis. Expert opinion: The development of novel drugs that antagonize the SPAK-WNK interaction, inhibit SPAK kinase activity, or disrupt SPAK kinase activation by interfering with its binding to MO25α/β could be useful adjuncts in essential hypertension, inflammatory colitis, and cystic fibrosis.en_GB
dc.description.sponsorshipThis paper was supported in part by NIH grant R21GM118944 to E. Delpire; and the March of Dimes Basil O’Connor Award, Simons Foundation SFARI Awardand NIH award (NRCDP K12) to K. T. Kahle.en_GB
dc.identifier.citationVol. 21 (8), pp. 795-804.en_GB
dc.identifier.doi10.1080/14728222.2017.1351949
dc.identifier.urihttp://hdl.handle.net/10871/33383
dc.language.isoenen_GB
dc.publisherTaylor & Francisen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/28679296en_GB
dc.rights© 2017 Informa UK Limited, trading as Taylor & Francis Group.en_GB
dc.subjectBlood pressure regulationen_GB
dc.subjectSPAK phosphorylationen_GB
dc.subjectcation-chloride cotransporters (CCCs)en_GB
dc.subjection homeostasisen_GB
dc.subjectkinase inhibitorsen_GB
dc.subjectsignal transductionen_GB
dc.titlePharmacological targeting of SPAK kinase in disorders of impaired epithelial transport.en_GB
dc.typeArticleen_GB
dc.date.available2018-07-06T08:54:48Z
dc.identifier.issn1472-8222
exeter.place-of-publicationEnglanden_GB
dc.descriptionThis is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.en_GB
dc.identifier.journalExpert Opinion on Therapeutic Targetsen_GB


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