title: Tyrosine 132 phosphorylation of influenza A virus M1 protein is crucial for virus replication by controlling the nuclear import of M1.
abstract: Phosphorylation of viral proteins plays important roles in the influenza A virus (IAV) life cycle. By using mass spectrometry, we identified tyrosine 132 (Y132) as a phosphorylation site of the matrix protein (M1) of the influenza virus A/WSN/1933(H1N1). Phosphorylation at this site is essential to the process of virus replication by controlling the nuclear import of M1. We further demonstrated that the phosphorylated tyrosine is crucial for the binding of M1 to the nuclear import factor importin-α1, since any substitutions at this site severely reduce this protein-protein interaction and damage the importin-α1-mediated nuclear import of M1. Additionally, the tyrosine phosphorylation which leads to the nuclear import of M1 is blocked by a Janus kinase inhibitor. The present study reveals a pivotal role of this tyrosine phosphorylation in the intracellular transportation of M1, which controls the process of viral replication.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Bi
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D010766:Phosphorylation; D011485:Protein Binding; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism
chemical_list: C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins; D028901:alpha Karyopherins; D014443:Tyrosine
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