{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:22:07Z","timestamp":1760217727210},"reference-count":47,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T00:00:00Z","timestamp":1445558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The importance of tyrosine kinases in airway smooth muscle (ASM) contraction is not fully understood. The aim of this study was to investigate the role of Src\u2010family kinases (SrcFK) and focal adhesion kinase (FAK) in GPCR\u2010mediated ASM contraction and associated signalling events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Contraction was recorded in intact or \u03b1\u2010toxin permeabilized rat bronchioles. Phosphorylation of SrcFK, FAK, myosin light\u2010chain\u201020 (MLC<jats:sub>20<\/jats:sub>) and myosin phosphatase targeting subunit\u20101 (MYPT\u20101) was evaluated in cultured human ASM cells (hASMC). [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was evaluated in Fura\u20102 loaded hASMC. Responses to carbachol (CCh) and bradykinin (BK) and the contribution of SrcFK and FAK to these responses were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Contractile responses in intact bronchioles were inhibited by antagonists of SrcFK, FAK and Rho\u2010kinase, while after \u03b1\u2010toxin permeabilization, they were sensitive to inhibition of SrcFK and Rho\u2010kinase, but not FAK. CCh and BK increased phosphorylation of MYPT\u20101 and MLC<jats:sub>20<\/jats:sub> and auto\u2010phosphorylation of SrcFK and FAK. MYPT\u20101 phosphorylation was sensitive to inhibition of Rho\u2010kinase and SrcFK, but not FAK. Contraction induced by SR Ca<jats:sup>2+<\/jats:sup> depletion and equivalent [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> responses in hASMC were sensitive to inhibition of both SrcFK and FAK, while depolarization\u2010induced contraction was sensitive to FAK inhibition only. SrcFK auto\u2010phosphorylation was partially FAK\u2010dependent, while FAK auto\u2010phosphorylation was SrcFK\u2010independent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>SrcFK mediates Ca<jats:sup>2+<\/jats:sup>\u2010sensitization in ASM, while SrcFK and FAK together and individually influence multiple Ca<jats:sup>2+<\/jats:sup> influx pathways. Tyrosine phosphorylation is therefore a key upstream signalling event in ASM contraction and may be a viable target for modulating ASM tone in respiratory disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13313","type":"journal-article","created":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T01:47:22Z","timestamp":1440121642000},"page":"5265-5280","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Divergent modulation of Rho\u2010kinase and Ca<sup>2+<\/sup> influx pathways by Src family kinases and focal adhesion kinase in airway smooth muscle"],"prefix":"10.1111","volume":"172","author":[{"given":"Yasin","family":"Shaifta","sequence":"first","affiliation":[{"name":"Division of Asthma, Allergy and Lung Biology, Faculty of Life Sciences and Medicine King's College London  London 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