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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-? (IFN-?R) and the ITAM adaptor Fc? as an example, we found that IFN-? modified responses of the phagocytic antibody receptor Fc?RI (CD64) to specify cell-autonomous antimicrobial functions. Unexpectedly, we also found that in peritoneal macrophages, IFN-?R itself required tonic signaling from Fc? through the kinase PI(3)K for the induction of a subset of IFN-?-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.

SUBMITTER: Bezbradica JS

PROVIDER: S-EPMC4137873 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Bezbradica Jelena S JS Rosenstein Rachel K RK DeMarco Richard A RA Brodsky Igor I Medzhitov Ruslan R

Nature immunology 20140309 4

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 modifi ...[more]

PMID: 24608040

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