Linked Life Data

20088952

Source:http://linkedlifedata.com/resource/pubmed/id/20088952

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-6-18
pubmed:abstractText
The non-structural protein 1 (A/NS1) of influenza A viruses (IAV) harbours several src-homology domain (SH) binding motifs that are required for interaction with cellular proteins. The SH3 binding motif at aa212-217 [PPLPPK] of A/NS1 was shown to be essential for binding to the cellular adaptor proteins CRK and CRKL. Both regulate diverse cellular effector pathways, including activation of the MAP-kinase JNK that in turn mediates antiviral responses to IAV infection. By studying functional consequences of A/NS1-CRK interaction we show here that A/NS1 binding to CRK contributes to suppression of the antiviral-acting JNK-ATF2 pathway. However, only IAV that encode an A/NS1-protein harbouring the CRK/CRKL SH3 binding motif PPLPPK were attenuated upon downregulation of CRKI/II and CRKL, but not of CRKII alone. The PPLPPK site-harbouring candidate strains could be discriminated from other strains by a pronounced viral activation of the JNK-ATF2 signalling module that was even further boosted upon knock-down of CRKI/II. Interestingly, this enhanced JNK activation did not alter type-I IFN-expression, but rather resulted in increased levels of virus-induced cell death. Our results imply that binding capacity of A/NS1 to CRK/CRKL has evolved in virus strains that over-induce the antiviral acting JNK-ATF2 signalling module and helps to suppress the detrimental apoptosis promoting action of this pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1462-5822
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
831-43
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
CRK adaptor protein expression is required for efficient replication of avian influenza A viruses and controls JNK-mediated apoptotic responses.
pubmed:affiliation
Institute of Molecular Virology, ZMBE, Muenster, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't