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NHERF1 is crucial to \u03b2\u20102\u2010adrenoceptor (\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    AR)\u2010mediated activation of cystic fibrosis transmembrane conductance regulator (CFTR) in epithelial cells, and NHERF1 has been proposed to mediate the recycling of internalized \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    AR back to the cell membrane. In the current study, we assessed the role of NHERF1 in regulating cAMP\u2010mediated signaling and immunomodulatory functions in airway smooth muscle (ASM). NHERF1 knockdown attenuated the induction of (protein kinase A) phospho\u2013vasodilator\u2010stimulated phosphoprotein (p\u2010VASP) by isoproterenol (ISO), prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ), or forskolin (FSK) as well as the induction of p\u2010heat shock protein 20 after 4 h of stimulation with ISO and FSK. NHERF1 knockdown fully abrogated the ISO\u2010, PGE\n                    <jats:sub>2<\/jats:sub>\n                    \u2010, and FSK\u2010induced IL\u20106 gene expression and cytokine production without affecting cAMP\u2010mediated phosphodiesterase 4D (PDE4D) gene expression, phospho\u2013cAMP response element\u2013binding protein (p\u2010CREB), and cAMP response element (CRE)\u2010Luc, or PDGF\u2010induced cyclin D1 expression. Interestingly, NHERF1 knockdown prevented ISO\u2010induced chromatin\u2010binding of the transcription factor CCAAT\u2010enhancer\u2013binding protein\u2010\u03b2 (c\/EBP\u03b2). c\/EBP\u03b2 knockdown almost completely abrogated the cAMP\u2010mediated IL\u20106 but not PDE4D gene expression. The differential regulation of cAMP\u2010induced signaling and gene expression in our study indicates a role for NHERF1 in the compartmentalization of cAMP signaling in ASM.\u2014Pera, T., Tompkins, E., Katz, M., Wang, B., Deshpande, D. A., Weinman, E. J., Penn, R. B. Specificity of NHERF1 regulation of GPCR signaling and function in human airway smooth muscle. FASEB J. 33, 9008\u20139016 (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.201900323r","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T16:11:35Z","timestamp":1556727095000},"page":"9008-9016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Specificity of NHERF1 regulation of GPCR signaling and function in human airway smooth muscle"],"prefix":"10.1096","volume":"33","author":[{"given":"Tonio","family":"Pera","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine Department of Medicine Center for Translational Medicine The Jane and Leonard Korman Respiratory Institute Thomas Jefferson University  Philadelphia Pennsylvania 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