| First Author | Bezbradica JS | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 4 | Pages | 333-42 |
| PubMed ID | 24608040 | Mgi Jnum | J:209615 |
| Mgi Id | MGI:5568184 | Doi | 10.1038/ni.2845 |
| Citation | Bezbradica JS, et al. (2014) A role for the ITAM signaling module in specifying cytokine-receptor functions. Nat Immunol 15(4):333-42 |
| abstractText | 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-gamma (IFN-gammaR) and the ITAM adaptor Fcgamma as an example, we found that IFN-gamma modified responses of the phagocytic antibody receptor FcgammaRI (CD64) to specify cell-autonomous antimicrobial functions. Unexpectedly, we also found that in peritoneal macrophages, IFN-gammaR itself required tonic signaling from Fcgamma through the kinase PI(3)K for the induction of a subset of IFN-gamma-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. |
