{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:56:31Z","timestamp":1791276991489,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Cell Biology (ASCB)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:p>Shear stress generated by distinct blood flow patterns modulates endothelial cell phenotype to spatially restrict atherosclerotic plaque development. Signaling through p21-activated kinase (PAK) mediates several of the deleterious effects of shear stress, including enhanced NF-\u03baB activation and proinflammatory gene expression. Whereas shear stress activates PAK in endothelial cells on a fibronectin matrix, basement membrane proteins limit shear-induced PAK activation and inflammation through a protein kinase A\u2013dependent pathway; however, the mechanisms underlying this regulation were unknown. We show that basement membrane proteins limit membrane recruitment of PAK2, the dominant isoform in endothelial cells, by blocking its interaction with the adaptor protein Nck. This uncoupling response requires protein kinase A\u2013dependent nitric oxide production and subsequent PAK2 phosphorylation on Ser-20 in the Nck-binding domain. Of importance, shear stress does not stimulate nitric oxide production in endothelial cells on fibronectin, resulting in enhanced PAK activation, NF-\u03baB phosphorylation, ICAM-1 expression, and monocyte adhesion. These data demonstrate that differential flow\u2013induced nitric oxide production regulates matrix-specific PAK signaling and describe a novel mechanism of nitric oxide\u2013dependent NF-\u03baB inhibition.<\/jats:p>","DOI":"10.1091\/mbc.e12-07-0513","type":"journal-article","created":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T20:15:00Z","timestamp":1353615300000},"page":"398-408","source":"Crossref","is-referenced-by-count":50,"title":["Altered nitric oxide production mediates matrix-specific PAK2 and NF-\u03baB activation by flow"],"prefix":"10.1091","volume":"24","author":[{"suffix":"Jr.","given":"Arif","family":"Yurdagul","sequence":"first","affiliation":[{"name":"Departments of Pathology, LSU Health Sciences Center, Shreveport, LA 71103"},{"name":"Cell Biology and Anatomy, LSU Health Sciences Center, Shreveport, LA 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Departments of Pathology, LSU Health Sciences Center, Shreveport, LA 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Daniel","family":"Funk","sequence":"additional","affiliation":[{"name":"Departments of Pathology, LSU Health Sciences Center, Shreveport, LA 71103"},{"name":"Cell Biology and Anatomy, LSU Health Sciences Center, Shreveport, LA 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Albert","sequence":"additional","affiliation":[{"name":"Departments of Pathology, LSU Health Sciences Center, Shreveport, LA 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Kevil","sequence":"additional","affiliation":[{"name":"Departments of Pathology, LSU Health Sciences Center, Shreveport, LA 71103"},{"name":"Cell Biology and Anatomy, LSU Health Sciences Center, Shreveport, LA 71103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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