A role for the ITAM signaling module in specifying cytokine-receptor functions.

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 Immunol

journal_title

Nature immunology

authors

Bezbradica JS,Rosenstein RK,DeMarco RA,Brodsky I,Medzhitov R

doi

10.1038/ni.2845

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

333-42

issue

4

eissn

1529-2908

issn

1529-2916

pii

ni.2845

journal_volume

15

pub_type

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