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

Bezbradica, Jelena S, Rosenstein, Rachel K, Demarco, Richard A, Brodsky, Igor and Medzhitov, Ruslan (2014) A role for the ITAM signaling module in specifying cytokine-receptor functions. Nature Immunology, 15 4: 333-342. doi:10.1038/ni.2845

Author Bezbradica, Jelena S
Rosenstein, Rachel K
Demarco, Richard A
Brodsky, Igor
Medzhitov, Ruslan
Title A role for the ITAM signaling module in specifying cytokine-receptor functions
Journal name Nature Immunology   Check publisher's open access policy
ISSN 1529-2916
Publication date 2014-04
Sub-type Article (original research)
DOI 10.1038/ni.2845
Open Access Status
Volume 15
Issue 4
Start page 333
End page 342
Total pages 10
Place of publication New York United States
Publisher Nature Publishing Group
Collection year 2015
Language eng
Subject 2403 Immunology
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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Citation counts: TR Web of Science Citation Count  Cited 19 times in Thomson Reuters Web of Science Article | Citations
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