Abstract:
:Diverse cellular responses to external cues are controlled by a small number of signal-transduction pathways, but how the specificity of functional outcomes is achieved remains unclear. Here we describe a mechanism for signal integration based on the functional coupling of two distinct signaling pathways widely used in leukocytes: the ITAM pathway and the Jak-STAT pathway. Through the use of the receptor for interferon-γ (IFN-γR) and the ITAM adaptor Fcγ as an example, we found that IFN-γ modified responses of the phagocytic antibody receptor FcγRI (CD64) to specify cell-autonomous antimicrobial functions. Unexpectedly, we also found that in peritoneal macrophages, IFN-γR itself required tonic signaling from Fcγ through the kinase PI(3)K for the induction of a subset of IFN-γ-specific antimicrobial functions. Our findings may be generalizable to other ITAM and Jak-STAT signaling pathways and may help explain signal integration by those pathways.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Bezbradica JS,Rosenstein RK,DeMarco RA,Brodsky I,Medzhitov Rdoi
10.1038/ni.2845subject
Has Abstractpub_date
2014-04-01 00:00:00pages
333-42issue
4eissn
1529-2908issn
1529-2916pii
ni.2845journal_volume
15pub_type
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