title: CDK/ERK-mediated phosphorylation of the human influenza A virus NS1 protein at threonine-215.
abstract: Posttranslational modification of viral proteins by cellular enzymes is a feature of many virus replication strategies. Here, we report that during infection the multifunctional human influenza A virus NS1 protein is phosphorylated at threonine-215. Substitution of alanine for threonine at this position reduced early viral propagation, an effect apparently unrelated to NS1 antagonizing host interferon responses or activating phosphoinositide 3-kinase signaling. In vitro, a subset of cellular proline-directed kinases, including cyclin dependent kinases (CDKs) and extracellular signal-regulated kinases (ERKs), potently phosphorylated NS1 protein at threonine-215. Our data suggest that CDK/ERK-mediated phosphorylation of NS1 at threonine-215 is important for efficient virus replication.
authors.affiliation: Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UK.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hale
authors.forename: Axel
authors.initials: A
authors.lastname: Knebel
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Botting
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Galloway
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Precious
authors.forename: David
authors.initials: D
authors.lastname: Jackson
authors.forename: Richard M
authors.initials: RM
authors.lastname: Elliott
authors.forename: Richard E
authors.initials: RE
authors.lastname: Randall
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D013912:Threonine / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D010948:Viral Plaque Assay; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D013912:Threonine; D018844:Cyclin-Dependent Kinases; D048049:Extracellular Signal-Regulated MAP Kinases