dc.contributor.author | Zhang, J | |
dc.contributor.author | Karimy, JK | |
dc.contributor.author | Delpire, E | |
dc.contributor.author | Kahle, KT | |
dc.date.accessioned | 2018-07-06T08:54:48Z | |
dc.date.issued | 2017-07-06 | |
dc.description.abstract | Introduction: 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.sponsorship | This 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.citation | Vol. 21 (8), pp. 795-804. | en_GB |
dc.identifier.doi | 10.1080/14728222.2017.1351949 | |
dc.identifier.uri | http://hdl.handle.net/10871/33383 | |
dc.language.iso | en | en_GB |
dc.publisher | Taylor & Francis | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/28679296 | en_GB |
dc.rights | © 2017 Informa UK Limited, trading as Taylor & Francis Group. | en_GB |
dc.subject | Blood pressure regulation | en_GB |
dc.subject | SPAK phosphorylation | en_GB |
dc.subject | cation-chloride cotransporters (CCCs) | en_GB |
dc.subject | ion homeostasis | en_GB |
dc.subject | kinase inhibitors | en_GB |
dc.subject | signal transduction | en_GB |
dc.title | Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-07-06T08:54:48Z | |
dc.identifier.issn | 1472-8222 | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record. | en_GB |
dc.identifier.journal | Expert Opinion on Therapeutic Targets | en_GB |