SOCS-1 binding to tyrosine 441 of IFN-γ receptor subunit 1 contributes to the attenuation of IFN-γ signaling in vivo

Abstract

Suppressor of cytokine signaling (SOCS)-1 is a critical inhibitor of IFN-γ signal transduction in vivo, but the precise biochemical mechanism of action of SOCS-1 is unclear. Studies in vitro have shown that SOCS-1 binds to Jaks and inhibits their catalytic activity, but recent studies indicate SOCS-1 may act in a similar manner to SOCS-3 by firstly interacting with cytokine receptors and then inhibiting Jak activity. Here, we have generated mice, termed Ifngr1441F, in which a putative SOCS-1 binding site, tyrosine 441 (Y441), on the IFN-γ receptor subunit 1 (IFNGR1) is mutated. We confirm that SOCS-1 binds to IFNGR1 in wild-type but not mutant cells. Mutation of Y441 results in impaired nega..