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Here we compared two medically relevant IAVs, namely A\/Hamburg\/4\/09 (H1N1<jats:sub>pdm09<\/jats:sub>) of the 2009 pandemic and the highly pathogenic avian IAV human isolate A\/Thailand\/1(KAN-1)\/2004 (H5N1), for their ability to trigger intracellular phosphorylation patterns using a highly sensitive peptide-based kinase activity profiling approach. Virus-dependent tyrosine phosphorylations of substrate peptides largely overlap between the two viruses and are also strongly overrepresented in comparison to serine\/threonine peptide phosphorylations. Both viruses trigger phosphorylations with distinct kinetics by overlapping and different kinases from which many form highly interconnected networks. As approximately half of the kinases forming a signalling hub have no known function for the IAV life cycle, we interrogated selected members of this group for their ability to interfere with IAV replication. These experiments revealed negative regulation of H1N1<jats:sub>pdm09<\/jats:sub> and H5N1 replication by NUAK [novel (nua) kinase] kinases and by redundant ephrin A (EphA) receptor tyrosine kinases.<\/jats:p>","DOI":"10.1099\/jgv.0.001762","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T15:16:16Z","timestamp":1656602176000},"source":"Crossref","is-referenced-by-count":4,"title":["Comparative kinase activity profiling of pathogenic influenza A viruses reveals new anti- and pro-viral protein kinases"],"prefix":"10.1099","volume":"103","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Medical Virology, Justus Liebig University Giessen, Germany"},{"name":"Institute of Biochemistry, Justus-Liebig-University Giessen (Germany), Member of the German Center for Lung Research, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Wei\u00df","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera Vivian","family":"Saul","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Justus-Liebig-University Giessen (Germany), Member of the German Center for Lung Research, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph Theo","family":"Schermuly","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Pleschka","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), partner site Giessen, Germany"},{"name":"Institute of Medical Virology, Justus Liebig University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-7192","authenticated-orcid":false,"given":"M. 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