title: The PDZ-ligand and Src-homology type 3 domains of epidemic avian influenza virus NS1 protein modulate human Src kinase activity during viral infection.
abstract: The Non-structural 1 (NS1) protein of avian influenza (AI) viruses is important for pathogenicity. Here, we identify a previously unrecognized tandem PDZ-ligand (TPL) domain in the extreme carboxy terminus of NS1 proteins from a subset of globally circulating AI viruses. By using protein arrays we have identified several human PDZ-cellular ligands of this novel domain, one of which is the RIL protein, a known regulator of the cellular tyrosine kinase Src. We found that the AI NS1 proteins bind and stimulate human Src tyrosine kinase, through their carboxy terminal Src homology type 3-binding (SHB) domain. The physical interaction between NS1 and Src and the ability of AI viruses to modulate the phosphorylation status of Src during the infection, were found to be influenced by the TPL arrangement. These results indicate the potential for novel host-pathogen interactions mediated by the TPL and SHB domains of AI NS1 protein.
authors: Institute of Molecular Genetics National Research Council, Pavia, Italy.
authors: Laura
authors: L
authors: Bavagnoli
authors: William G
authors: WG
authors: Dundon
authors: Anna
authors: A
authors: Garbelli
authors: Bianca
authors: B
authors: Zecchin
authors: Adelaide
authors: A
authors: Milani
authors: Geetha
authors: G
authors: Parakkal
authors: Fausto
authors: F
authors: Baldanti
authors: Stefania
authors: S
authors: Paolucci
authors: Romain
authors: R
authors: Volmer
authors: Yizeng
authors: Y
authors: Tu
authors: Chuanyue
authors: C
authors: Wu
authors: Ilaria
authors: I
authors: Capua
authors: Giovanni
authors: G
authors: Maga
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D058872:Epidemics; D006801:Humans; D057916:Influenza A Virus, H7N1 Subtype; D005585:Influenza in Birds / Q000821:virology*; D060588:LIM Domain Proteins / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D054731:PDZ Domains; D040081:Protein Array Analysis; D054730:Protein Interaction Domains and Motifs; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C085820:INS1 protein, influenza virus; D060588:LIM Domain Proteins; D008024:Ligands; C486247:PDLIM4 protein, human; D017361:Viral Nonstructural Proteins; D019061:src-Family Kinases