tetano
Editor, Senior Moderator
Cell Microbiol. 2014 Jul 23. doi: 10.1111/cmi.12332. [Epub ahead of print]
Avian influenza viruses inhibit the major cellular signaling integrator c-Abl.
Hrincius ER1, Liedmann S, Anhlan D, Wolff T, Ludwig S, Ehrhardt C.
Author information
Abstract
The non-structural protein 1 (NS1) of influenza A viruses (IAV) encodes several src homology (SH) binding motifs (bm) (one SH2bm, up to two SH3bm), which mediate interactions with host cell proteins. In contrast to NS1 of human IAV, NS1 of avian strains possess the second SH3bm (SH3(II)bm) consensus sequence. Since our former studies demonstrated an NS1-CRK interaction, mediated by this motif, here, we addressed the regulatory properties of this SH3bm for cellular signaling. Initially, we observed a reduced basal CRK phosphorylation upon infection with avian IAV harboring an NS1 with an SH3(II)bm in contrast to human IAV. Reduced activity of the tyrosine kinase c-Abl was identified to be responsible for reduced CRK phosphorylation. Further, binding of NS1 to c-Abl was determined, and mutational manipulation of the SH3(II)bm illustrated the necessity of this motif for c-Abl inhibition. Interestingly, Abl kinase inhibition resulted in impaired avian IAV propagation and pathogenicity and mutational analysis linked the pronounced inhibition of c-Abl to cytopathogenic cell alterations upon avian IAV infections. Taken together, NS1 proteins of avian IAV interfere with the kinase activity of c-Abl, a major cellular signaling integrator that controls multiple signaling processes and cell fate regulations apparently including IAV infections.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Abl kinase; NS1 protein; SH binding motif; cellular signal transduction; influenza A virus
PMID:
25052580
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25052580
Avian influenza viruses inhibit the major cellular signaling integrator c-Abl.
Hrincius ER1, Liedmann S, Anhlan D, Wolff T, Ludwig S, Ehrhardt C.
Author information
Abstract
The non-structural protein 1 (NS1) of influenza A viruses (IAV) encodes several src homology (SH) binding motifs (bm) (one SH2bm, up to two SH3bm), which mediate interactions with host cell proteins. In contrast to NS1 of human IAV, NS1 of avian strains possess the second SH3bm (SH3(II)bm) consensus sequence. Since our former studies demonstrated an NS1-CRK interaction, mediated by this motif, here, we addressed the regulatory properties of this SH3bm for cellular signaling. Initially, we observed a reduced basal CRK phosphorylation upon infection with avian IAV harboring an NS1 with an SH3(II)bm in contrast to human IAV. Reduced activity of the tyrosine kinase c-Abl was identified to be responsible for reduced CRK phosphorylation. Further, binding of NS1 to c-Abl was determined, and mutational manipulation of the SH3(II)bm illustrated the necessity of this motif for c-Abl inhibition. Interestingly, Abl kinase inhibition resulted in impaired avian IAV propagation and pathogenicity and mutational analysis linked the pronounced inhibition of c-Abl to cytopathogenic cell alterations upon avian IAV infections. Taken together, NS1 proteins of avian IAV interfere with the kinase activity of c-Abl, a major cellular signaling integrator that controls multiple signaling processes and cell fate regulations apparently including IAV infections.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Abl kinase; NS1 protein; SH binding motif; cellular signal transduction; influenza A virus
PMID:
25052580
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25052580