{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:36:24Z","timestamp":1790775384096,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It has been reported that actin polymerization is regulated by protein tyrosine phosphorylation in smooth muscle on contractile stimulation. The role of protein serine\/threonine phosphorylation in modulating actin dynamics is underinvestigated. SLK (Ste20-like kinase) is a serine\/threonine protein kinase that plays a role in apoptosis, cell cycle, proliferation, and migration. The function of SLK in smooth muscle is mostly unknown. Here, SLK knockdown (KD) inhibited acetylcholine (ACh)-induced actin polymerization and contraction without affecting myosin light chain phosphorylation at Ser-19 in human airway smooth muscle. Stimulation with ACh induced paxillin phosphorylation at Ser-272, which was reduced in SLK KD cells. However, SLK did not catalyze paxillin Ser-272 phosphorylation in vitro. But, SLK KD attenuated Plk1 (polo-like kinase 1) phosphorylation at Thr-210. Plk1 mediated paxillin phosphorylation at Ser-272 in vitro. Expression of the nonphosphorylatable paxillin mutant S272A (substitution of alanine at Ser-272) attenuated the agonist-enhanced F-actin\/G-actin ratios without affecting myosin light chain phosphorylation. Because N-WASP (neuronal Wiskott-Aldrich Syndrome Protein) phosphorylation at Tyr-256 (an indication of its activation) promotes actin polymerization, we also assessed the role of paxillin phosphorylation in N-WASP activation. S272A paxillin inhibited the ACh-enhanced N-WASP phosphorylation at Tyr-256. Together, these results suggest that SLK regulates paxillin phosphorylation at Ser-272 via Plk1, which modulates N-WASP activation and actin polymerization in smooth muscle. SLK-mediated actin cytoskeletal reorganization may facilitate force transmission between the contractile units and the extracellular matrix.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0310oc","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T16:10:38Z","timestamp":1578499838000},"page":"645-656","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":25,"title":["Ste20-like Kinase\u2013mediated Control of Actin Polymerization Is a New Mechanism for Thin Filament\u2013associated Regulation of Airway Smooth Muscle Contraction"],"prefix":"10.1093","volume":"62","author":[{"given":"Yinna","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-9249","authenticated-orcid":false,"given":"Dale D.","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,1]]},"reference":[{"key":"2026021100431802700_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apha.2017.06.001","article-title":"The dynamic actin cytoskeleton in smooth muscle","volume":"81","author":"Tang","year":"2018","journal-title":"Adv Pharmacol"},{"key":"2026021100431802700_bib2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s12931-015-0296-1","article-title":"Critical role of actin-associated proteins in smooth muscle contraction, cell proliferation, airway hyperresponsiveness and airway remodeling","volume":"16","author":"Tang","year":"2015","journal-title":"Respir Res"},{"key":"2026021100431802700_bib3","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1165\/rcmb.2014-0125OC","article-title":"Glia maturation factor-\u03b3 phosphorylation at Tyr-104 regulates actin dynamics and contraction in human airway smooth muscle","volume":"51","author":"Wang","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026021100431802700_bib4","doi-asserted-by":"crossref","first-page":"14157","DOI":"10.1074\/jbc.M114.548099","article-title":"The association of cortactin with profilin-1 is critical for smooth muscle contraction","volume":"289","author":"Wang","year":"2014","journal-title":"J Biol Chem"},{"key":"2026021100431802700_bib5","doi-asserted-by":"crossref","first-page":"20713","DOI":"10.1074\/jbc.M112.439877","article-title":"Role of the adapter protein Abi1 in actin-associated signaling and smooth muscle contraction","volume":"288","author":"Wang","year":"2013","journal-title":"J Biol Chem"},{"key":"2026021100431802700_bib6","doi-asserted-by":"crossref","first-page":"C576","DOI":"10.1152\/ajpcell.00253.2008","article-title":"Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction","volume":"295","author":"Gunst","year":"2008","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026021100431802700_bib7","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1113\/jphysiol.2012.232306","article-title":"Deciphering actin cytoskeletal function in the contractile vascular smooth muscle cell","volume":"590","author":"Yamin","year":"2012","journal-title":"J Physiol"},{"key":"2026021100431802700_bib8","doi-asserted-by":"crossref","first-page":"C559","DOI":"10.1152\/ajpcell.00431.2009","article-title":"Actin polymerization in differentiated vascular smooth muscle cells requires vasodilator-stimulated phosphoprotein","volume":"298","author":"Kim","year":"2010","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026021100431802700_bib9","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1096\/cj.01-0104hyp","article-title":"Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior","volume":"16","author":"Cipolla","year":"2002","journal-title":"FASEB J"},{"key":"2026021100431802700_bib10","doi-asserted-by":"crossref","first-page":"L1161","DOI":"10.1152\/ajplung.00298.2003","article-title":"Electron microscopic study of actin polymerization in airway smooth muscle","volume":"286","author":"Herrera","year":"2004","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026021100431802700_bib11","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1083\/jcb.201401049","article-title":"SLK-dependent activation of ERMs controls LGN-NuMA localization and spindle orientation","volume":"205","author":"Machicoane","year":"2014","journal-title":"J Cell Biol"},{"key":"2026021100431802700_bib12","doi-asserted-by":"crossref","first-page":"7566","DOI":"10.1038\/sj.onc.1203119","article-title":"Induction of apoptosis by SLK, a Ste20-related kinase","volume":"18","author":"Sabourin","year":"1999","journal-title":"Oncogene"},{"key":"2026021100431802700_bib13","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/cm.21276","article-title":"SLK\/LOSK kinase regulates cell motility independently of microtubule organization and Golgi polarization","volume":"73","author":"Fokin","year":"2016","journal-title":"Cytoskeleton (Hoboken)"},{"key":"2026021100431802700_bib14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/cam.22495","article-title":"Ste20-like kinase SLK, at the crossroads: a matter of life and death","volume":"7","author":"Al-Zahrani","year":"2013","journal-title":"Cell Adhes Migr"},{"key":"2026021100431802700_bib15","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1046\/j.1365-2443.2000.00337.x","article-title":"Ste20-like kinase (SLK), a regulatory kinase for polo-like kinase (Plk) during the G2\/M transition in somatic cells","volume":"5","author":"Ellinger-Ziegelbauer","year":"2000","journal-title":"Genes Cells"},{"key":"2026021100431802700_bib16","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrm1401","article-title":"Polo-like kinases and the orchestration of cell division","volume":"5","author":"Barr","year":"2004","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026021100431802700_bib17","doi-asserted-by":"crossref","first-page":"23693","DOI":"10.1074\/jbc.M116.749341","article-title":"Polo-like kinase 1 regulates vimentin phosphorylation at ser-56 and contraction in smooth muscle","volume":"291","author":"Li","year":"2016","journal-title":"J Biol Chem"},{"key":"2026021100431802700_bib18","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1242\/jcs.018044","article-title":"Paxillin comes of age","volume":"121","author":"Deakin","year":"2008","journal-title":"J Cell Sci"},{"key":"2026021100431802700_bib19","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12931-017-0544-7","article-title":"The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration","volume":"18","author":"Tang","year":"2017","journal-title":"Respir Res"},{"key":"2026021100431802700_bib20","doi-asserted-by":"crossref","first-page":"C993","DOI":"10.1152\/ajpcell.00090.2007","article-title":"Paxillin phosphorylation, actin polymerization, noise temperature, and the sustained phase of swine carotid artery contraction","volume":"293","author":"Rembold","year":"2007","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026021100431802700_bib21","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1083\/jcb.200509075","article-title":"Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics","volume":"173","author":"Nayal","year":"2006","journal-title":"J Cell Biol"},{"key":"2026021100431802700_bib22","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1113\/JP272132","article-title":"p21-Activated kinase (Pak) regulates airway smooth muscle contraction by regulating paxillin complexes that mediate actin polymerization","volume":"594","author":"Zhang","year":"2016","journal-title":"J Physiol"},{"key":"2026021100431802700_bib23","doi-asserted-by":"crossref","first-page":"8913","DOI":"10.1074\/jbc.M114.621003","article-title":"Recruitment of \u03b2-catenin to N-cadherin is necessary for smooth muscle contraction","volume":"290","author":"Wang","year":"2015","journal-title":"J Biol Chem"},{"key":"2026021100431802700_bib24","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1165\/rcmb.2012-0315OC","article-title":"Raf-1, actin dynamics, and abelson tyrosine kinase in human airway smooth muscle cells","volume":"48","author":"Wang","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026021100431802700_bib25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12931-017-0709-4","article-title":"Role and regulation of Abelson tyrosine kinase in Crk-associated substrate\/profilin-1 interaction and airway smooth muscle contraction","volume":"19","author":"Wang","year":"2018","journal-title":"Respir Res"},{"key":"2026021100431802700_bib26","doi-asserted-by":"crossref","first-page":"12635","DOI":"10.1038\/s41598-018-30895-8","article-title":"Microrna mir-509 regulates erk1\/2, the vimentin network, and focal adhesions by targeting plk1","volume":"8","author":"Liao","year":"2018","journal-title":"Sci Rep"},{"key":"2026021100431802700_bib27","first-page":"jcs222380","article-title":"Specific protein 1, c-Abl and ERK1\/2 form a regulatory loop","volume":"132","author":"Long","year":"2019","journal-title":"J Cell Sci"},{"key":"2026021100431802700_bib28","doi-asserted-by":"crossref","first-page":"11403","DOI":"10.1074\/jbc.M115.645788","article-title":"Vasodilator-stimulated phosphoprotein (VASP) regulates actin polymerization and contraction in airway smooth muscle by a vinculin-dependent mechanism","volume":"290","author":"Wu","year":"2015","journal-title":"J Biol Chem"},{"key":"2026021100431802700_bib29","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1074\/jbc.M110.139923","article-title":"Activation of vinculin induced by cholinergic stimulation regulates contraction of tracheal smooth muscle tissue","volume":"286","author":"Huang","year":"2011","journal-title":"J Biol Chem"},{"key":"2026021100431802700_bib30","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1161\/CIRCRESAHA.107.156463","article-title":"Abl silencing inhibits CAS-mediated process and constriction in resistance arteries","volume":"101","author":"Anfinogenova","year":"2007","journal-title":"Circ Res"},{"key":"2026021100431802700_bib31","doi-asserted-by":"crossref","first-page":"34716","DOI":"10.1074\/jbc.M607715200","article-title":"Critical role of vimentin phosphorylation at Ser-56 by p21-activated kinase in vimentin cytoskeleton signaling","volume":"281","author":"Li","year":"2006","journal-title":"J Biol Chem"},{"key":"2026021100431802700_bib32","doi-asserted-by":"crossref","first-page":"L240","DOI":"10.1152\/ajplung.00199.2006","article-title":"Dissociation of Crk-associated substrate from the vimentin network is regulated by p21-activated kinase on ACh activation of airway smooth muscle","volume":"292","author":"Wang","year":"2007","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026021100431802700_bib33","doi-asserted-by":"crossref","first-page":"C483","DOI":"10.1152\/ajpcell.00097.2006","article-title":"Role of vimentin in smooth muscle force development","volume":"291","author":"Wang","year":"2006","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026021100431802700_bib34","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/nm.4364","article-title":"Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis","volume":"23","author":"de C\u00e1rcer","year":"2017","journal-title":"Nat Med"},{"key":"2026021100431802700_bib35","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1083\/jcb.200403127","article-title":"Regulation of WASP\/WAVE proteins: making a long story short","volume":"166","author":"Bompard","year":"2004","journal-title":"J Cell Biol"},{"key":"2026021100431802700_bib36","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1161\/CIRCRESAHA.107.164764","article-title":"Ste20-related kinase SLK phosphorylates Ser188 of RhoA to induce vasodilation in response to angiotensin II Type 2 receptor activation","volume":"102","author":"Guilluy","year":"2008","journal-title":"Circ Res"},{"key":"2026021100431802700_bib37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1139\/cjpp-2014-0388","article-title":"A novel role for RhoA GTPase in the regulation of airway smooth muscle contraction","volume":"93","author":"Zhang","year":"2015","journal-title":"Can J Physiol Pharmacol"},{"key":"2026021100431802700_bib38","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1098\/rstb.2004.1562","article-title":"Smooth muscle myosin: regulation and properties","volume":"359","author":"Somlyo","year":"2004","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2026021100431802700_bib39","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.cellsig.2012.12.019","article-title":"p130Cas: a key signalling node in health and disease","volume":"25","author":"Barrett","year":"2013","journal-title":"Cell Signal"},{"key":"2026021100431802700_bib40","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/S1357-2725(02)00259-5","article-title":"Airway smooth muscle: contraction and beyond","volume":"35","author":"Amrani","year":"2003","journal-title":"Int J Biochem Cell Biol"},{"key":"2026021100431802700_bib41","doi-asserted-by":"crossref","first-page":"G849","DOI":"10.1152\/ajpgi.00530.2004","article-title":"Signal-transduction pathways that regulate visceral smooth muscle function. III. Coupling of muscarinic receptors to signaling kinases and effector proteins in gastrointestinal smooth muscles","volume":"288","author":"Gerthoffer","year":"2005","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026021100431802700_bib42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1365-2885.2008.00944.x","article-title":"Serotonin: a review","volume":"31","author":"Mohammad-Zadeh","year":"2008","journal-title":"J Vet Pharmacol Ther"},{"key":"2026021100431802700_bib43","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0026-895X(24)26493-2","article-title":"Up-regulation of airway smooth muscle histamine H(1) receptor mRNA, protein, and function by beta(2)-adrenoceptor activation","volume":"57","author":"Mak","year":"2000","journal-title":"Mol Pharmacol"},{"key":"2026021100431802700_bib44","first-page":"275","article-title":"Pharmacological properties of histamine receptor subtypes","volume":"40","author":"Arrang","year":"1994","journal-title":"Cell Mol Biol"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/62\/5\/645\/66763667\/ajrcmb_62_5_645.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/62\/5\/645\/66763667\/ajrcmb_62_5_645.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T05:43:27Z","timestamp":1770788607000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/62\/5\/645\/8461498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,1]]},"references-count":44,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5,1]]},"published-print":{"date-parts":[[2020,5,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2019-0310oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5]]},"published":{"date-parts":[[2020,5,1]]},"assertion":[{"value":"2019-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}