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Publication : Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells.

First Author  Rajasekaran K Year  2013
Journal  Nat Immunol Volume  14
Issue  11 Pages  1127-36
PubMed ID  24036998 Mgi Jnum  J:208208
Mgi Id  MGI:5562484 Doi  10.1038/ni.2708
Citation  Rajasekaran K, et al. (2013) Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells. Nat Immunol 14(11):1127-36
abstractText  Inflammation is a critical component of the immune response. However, acute or chronic inflammation can be highly destructive. Uncontrolled inflammation forms the basis for allergy, asthma and various autoimmune disorders. Here we identified a signaling pathway that was exclusively responsible for the production of inflammatory cytokines but not for cytotoxicity. Recognition of tumor cells expressing the NK cell-activatory ligands H60 or CD137L by mouse natural killer (NK) cells led to efficient cytotoxicity and the production of inflammatory cytokines. Both of those effector functions required the kinases Lck, Fyn and PI(3)K (subunits p85alpha and p110delta) and the signaling protein PLC-gamma2. However, a complex of Fyn and the adaptor ADAP exclusively regulated the production of inflammatory cytokines but not cytotoxicity in NK cells. That unique function of ADAP required a Carma1-Bcl-10-MAP3K7 signaling axis. Our results have identified molecules that can be targeted to regulate inflammation without compromising NK cell cytotoxicity.
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