{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:50:40Z","timestamp":1790373040736,"version":"4.1.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2003,2,1]]},"abstract":"<jats:p> Activation of airway epithelial Na-K-2Cl cotransporter (NKCC)1 requires increased activity of protein kinase C (PKC)-\u03b4, which localizes predominantly to the actin cytoskeleton. Prompted by reports of a role for actin in NKCC1 function, we studied a signaling mechanism linking NKCC1 and PKC. Stabilization of actin polymerization with jasplakinolide increased activity of NKCC1, whereas inhibition of actin polymerization with latrunculin B prevented hormonal activation of NKCC1. Protein-protein interactions among NKCC1, actin, and PKC-\u03b4 were verified by Western blot analysis of immunoprecipitated proteins. PKC-\u03b4 was detected in immunoprecipitates of NKCC1 and vice versa. Actin was also detected in immunoprecipitates of NKCC1 and PKC-\u03b4. Pulldown of endogenous actin revealed the presence of NKCC1 and PKC-\u03b4. Binding of recombinant PKC-\u03b4 to NKCC1 was not detected in overlay assays. Rather, activated PKC-\u03b4 bound to actin, and this interaction was prevented by a peptide encoding \u03b4C2, a C2-like domain based on the amino acid sequence of PKC-\u03b4. \u03b4C2 also blocked stimulation of NKCC1 function by methoxamine. Immunofluorescence and confocal microscopy revealed PKC-\u03b4 in the cytosol and cell periphery. Merged images of cells stained for actin and PKC-\u03b4 indicated colocalization of PKC-\u03b4 and actin at the cell periphery. The results indicate that actin is critical for the activation of NKCC1 through a direct interaction with PKC-\u03b4. <\/jats:p>","DOI":"10.1152\/ajpcell.00357.2002","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T00:12:39Z","timestamp":1368490359000},"page":"C487-C496","source":"Crossref","is-referenced-by-count":51,"title":["Stability of actin cytoskeleton and PKC-\u03b4 binding to actin  regulate NKCC1 function in airway epithelial cells"],"prefix":"10.1152","volume":"284","author":[{"given":"Carole M.","family":"Liedtke","sequence":"first","affiliation":[{"name":"Warren Alan Bernbaum, M.D. Center for Cystic Fibrosis Research, Department of Pediatrics, Rainbow Babies & Children Hospital, and Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4948"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Hubbard","sequence":"additional","affiliation":[{"name":"Warren Alan 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