{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:22:17Z","timestamp":1774686137121,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["I01BX007080"],"award-info":[{"award-number":["I01BX007080"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u03b2-adrenergic receptor (\u03b2AR) activation promotes relaxation of both vascular and airway smooth muscle cells (VSMCs and ASMCs, respectively), though the signaling mechanisms have not been fully elucidated. We previously found that the activity of Kv7.5 voltage-activated potassium channels in VSMCs is robustly enhanced by activation of \u03b2ARs via a mechanism involving protein kinase A (PKA)-dependent phosphorylation. We also found that enhancement of Kv7 channel activity in ASMCs promotes airway relaxation. Here we provide evidence that Kv7.5 channels are natively expressed in primary cultures of human ASMCs and that they conduct currents which are robustly enhanced in response to activation of the \u03b2AR\/cyclic adenosine monophosphate (cAMP)\/PKA pathway. MIT Scansite software analysis of putative PKA phosphorylation sites on Kv7.5 identified 8 candidate serine or threonine residues. Each residue was individually mutated to an alanine to prevent its phosphorylation and then tested for responses to \u03b2AR activation or to stimuli that elevate cAMP levels. Only the mutation of serine 53 (S53A), located on the amino terminus of Kv7.5, significantly reduced the increase in Kv7.5 current in response to these stimuli. A phospho-mimic mutation (S53D) exhibited characteristics of \u03b2AR-activated Kv7.5. Serine-to-alanine mutations of 6 putative PKA phosphorylation sites on the Kv7.5 C-terminus, individually or in combination, did not significantly reduce the enhancement of the currents in response to forskolin treatment (to elevate cAMP levels). We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to \u03b2AR activation in vascular and airway smooth muscle cells.<\/jats:p>","DOI":"10.3390\/ijms19082223","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T11:55:08Z","timestamp":1532951708000},"page":"2223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mechanisms of PKA-Dependent Potentiation of Kv7.5 Channel Activity in Human Airway Smooth Muscle Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Lyubov I.","family":"Brueggemann","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology &amp; Therapeutics, Loyola University Chicago, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne L.","family":"Cribbs","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Loyola University Chicago, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minhua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology &amp; Therapeutics, Loyola University Chicago, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Kouta","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology &amp; Therapeutics, Loyola University Chicago, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3875-9667","authenticated-orcid":false,"given":"Kenneth L.","family":"Byron","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology &amp; Therapeutics, Loyola University Chicago, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1113\/jphysiol.2008.153007","article-title":"Kv7 (KCNQ) potassium channels that are mutated in human diseases","volume":"586","author":"Brown","year":"2008","journal-title":"J. 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