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The PDZ-ligand and Src-homology type 3 domains of epidemic avian influenza virus NS1 protein modulate human Src kinase activity during viral infection

Bavagnoli, L and Dundon, WG and Garbelli, A and Zecchin, B and Milani, A and Parakkal, G and Baldanti, F and Paolucci, S and Volmer, R and Tu, Y and Wu, C and Capua, I and Maga, G (2011) The PDZ-ligand and Src-homology type 3 domains of epidemic avian influenza virus NS1 protein modulate human Src kinase activity during viral infection. PLoS ONE, 6 (11).

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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. © 2011 Bavagnoli et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bavagnoli, L
Dundon, WG
Garbelli, A
Zecchin, B
Milani, A
Parakkal, G
Baldanti, F
Paolucci, S
Volmer, R
Tu, Yyizengtu@pitt.eduYIZENGTU
Wu, Ccarywu@pitt.eduCARYWU
Capua, I
Maga, G
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorPekosz, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 14 November 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 11
DOI or Unique Handle: 10.1371/journal.pone.0027789
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
MeSH Headings: Amino Acid Sequence; Animals; Birds; Cell Line; DNA-Binding Proteins--metabolism; Epidemics; Humans; Influenza A Virus, H7N1 Subtype; Influenza in Birds--virology; LIM Domain Proteins--metabolism; Ligands; Molecular Sequence Data; PDZ Domains; Protein Array Analysis; Protein Interaction Domains and Motifs; Viral Nonstructural Proteins--chemistry; Viral Nonstructural Proteins--metabolism; src Homology Domains; src-Family Kinases--metabolism
Other ID: NLM PMC3215730
PubMed Central ID: PMC3215730
PubMed ID: 22110760
Date Deposited: 07 Sep 2012 20:34
Last Modified: 22 Jan 2019 20:55
URI: http://d-scholarship.pitt.edu/id/eprint/13995

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