Complex regulation of the Csk homologous kinase (Chk) by IL-4 family cytokines and IFN-γ in human peripheral blood monocytes

Csk homologous kinase (Chk) is a tyrosine kinase that shares homology with Csk and, like Csk, has the potential to inhibit src-family kinase function through phosphorylation. In myeloid lineage cells, Chk expression is dependent on monocytic differentiation. IL-4 and IL-13 are cytokines involved in monocytic differentiation that have recently been shown to induce Chk expression in peripheral blood monocytes (PBMs). In this study, we show that two other members of the IL-4 family, IL-3 and GM-CSF, can also induce Chk expression at RNA and protein levels. Interestingly, Chk induction is both blocked and reversed by IFN-γ treatment. Additionally, a short pretreatment with IFN-γ is sufficient to prevent Chk induction, and the effects of IFN-γ are dependent on protein synthesis. Collectively, these results suggest that activation of Chk expression and signaling may have a role in the IL-4 family-mediated differentiation of myeloid cells, and inhibition of Chk activation may be one mechanism by which IFN-γ alters IL-4-mediated affects.