{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:47:36Z","timestamp":1791103656746,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rhinovirus (RV) is responsible for the majority of common colds and triggers exacerbations of asthma and chronic obstructive lung disease. We have shown that RV serotype 39 (RV39) infection activates phosphatidylinositol 3 (PI 3)-kinase and the serine threonine kinase Akt minutes after infection and that the activation of PI 3-kinase and Akt is required for maximal interleukin-8 (IL-8) expression. Here, we further examine the contributions of Src and PI 3-kinase activation to RV-induced Akt activation and IL-8 expression. Confocal fluorescent microscopy of 16HBE14o\u2212 human bronchial epithelial cells showed rapid (10-min) colocalization of RV39 with Src, p85\u03b1 PI 3-kinase, p110\u03b2 PI 3-kinase, Akt and Cit-Akt-PH, a fluorescent Akt pleckstrin homology domain which binds PI(3,4,5)P\n                    <jats:sub>3<\/jats:sub>\n                    . The chemical Src inhibitor PP2 {4-amino-5-(4-chlorophenyl)-7-(\n                    <jats:italic>t<\/jats:italic>\n                    -butyl)pyrazolo [3,4-\n                    <jats:italic>d<\/jats:italic>\n                    ]pyrimidine} and the PI 3-kinase inhibitor LY294002 each inhibited Akt phosphorylation and the colocalization of RV39 with Akt. Digoxigenin-tagged RV coprecipitated with a Crosstide kinase likely to be Akt, and inhibition of Src blocked kinase activity. Digoxigenin-tagged RV39 colocalized with the lipid raft marker ceramide. In 16HBE14o\u2212 and primary mucociliary differentiated human bronchial epithelial cells, inhibition of Src kinase activity with the Src family chemical inhibitor PP2, dominant-negative Src (K297R), and Src small interfering RNA (siRNA) each inhibited RV39-induced IL-8 expression. siRNA against p110\u03b2 PI 3-kinase also inhibited IL-8 expression. These data demonstrate that, in the context of RV infection, Src and p110\u03b2 PI 3-kinase are upstream activators of Akt and the IL-8 promoter and that RV colocalizes with Src, PI 3-kinase, and Akt in lipid rafts.\n                  <\/jats:p>","DOI":"10.1128\/jvi.02309-06","type":"journal-article","created":{"date-parts":[[2006,11,22]],"date-time":"2006-11-22T20:28:59Z","timestamp":1164227339000},"page":"1186-1194","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Rhinovirus Activates Interleukin-8 Expression via a Src\/p110\u03b2 Phosphatidylinositol 3-Kinase\/Akt Pathway in Human Airway Epithelial Cells"],"prefix":"10.1128","volume":"81","author":[{"given":"J. Kelley","family":"Bentley","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn C.","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jia","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma S.","family":"Sajjan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc B.","family":"Hershenson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Communicable Diseases"},{"name":"Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.2.2003122"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324059"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.11.5944"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.31.19236"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.10.1.7507342"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/378785a0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.3375"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.1.9808074"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.6.2003019"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.01.99114901"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500835200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.2.9610079"},{"key":"e_1_3_2_14_2","first-page":"36","volume":"27","year":"1997","unstructured":"Grunberg, K., M. C. Timmers, H. H. Smits, E. P. de Klerk, E. C. Dick, W. J. Spaan, P. S. Hiemstra, and P. J. Sterk. 1997. Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo. Clin. Exp. Allergy27:36-45.","journal-title":"Clin. Exp. Allergy"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410592200"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.14.7937"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.695"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.310.6989.1225"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104018200"},{"key":"e_1_3_2_20_2","first-page":"117","volume":"8","year":"1993","unstructured":"MacAuley, A., M. Okada, S. Nada, H. Nakagawa, and J. A. Cooper. 1993. Phosphorylation of Src mutants at Tyr 527 in fibroblasts does not correlate with in vitro phosphorylation by CSK. 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