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To date, there are no effective therapies to combat ASM cell proliferation, which contributes to bronchoconstriction and airway obstruction. Growth factors such as platelet\u2010derived growth factor (PDGF) and the activation of the ERK1\/2 are major regulators of ASM cell proliferation and airway remodeling in asthma. However, given the ubiquitous expression and multiple functions of ERK1\/2, complete inhibition of ERK1\/2 using ATP\u2010competitive inhibitors may lead to unwanted off\u2010target effects. Alternatively, we have identified compounds that are designed to target substrate docking sites and act as function\u2010selective inhibitors of ERK1\/2 signaling. Here, we show that both function\u2010selective and ATP\u2010competitive ERK1\/2 inhibitors are effective at inhibiting PDGF\u2010mediated proliferation, collagen production, and IL\u20106 secretion in ASM cells. Proteomic analysis revealed that both types of inhibitors had similar effects on reducing proteins related to TGF\u2010\u03b2 and IL\u20106 signaling that are relevant to airway remodeling. However, function\u2010selective ERK1\/2 inhibitors caused fewer changes in protein expression compared with ATP\u2010competitive inhibitors. These studies provide a molecular basis for the development of function\u2010selective ERK1\/2 inhibitors to mitigate airway remodeling in asthma with defined regulation of ERK1\/2 signaling.\u2014Defnet, A. E., Huang, W., Polischak, S., Yadav, S. K., Kane, M. A., Shapiro, P., Deshpande, D. A. Effects of ATP\u2010competitive and function\u2010selective ERK inhibitors on airway smooth muscle cell proliferation. FASEB J. 33, 10833\u201310843 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900680r","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T21:19:37Z","timestamp":1562102377000},"page":"10833-10843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Effects of ATP\u2010competitive and function\u2010selective ERK inhibitors on airway smooth muscle cell proliferation"],"prefix":"10.1096","volume":"33","author":[{"given":"Amy E.","family":"Defnet","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiliang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Polischak","sequence":"additional","affiliation":[{"name":"Department of Medicine Jefferson University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Medicine Jefferson University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen A.","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Maryland Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak A.","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Department of Medicine Jefferson University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(02)00259-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00008109"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.129429"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2006.04.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5622fje"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.23.4.4115"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200705-063VS"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0510734"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1569-9048(03)00154-X"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1999.277.3.L479"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.04.039"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21450"},{"issue":"2","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1164\/ajrccm.164.supplement_2.2106059","article-title":"Mechanisms of airway remodeling. 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