Figure 4.

(A) Specificity of cytokine–STAT signaling. Cell-specific cytokine signals result, at least in part, from the receptors that are expressed on a cell and the ligands it encounters. Each ligand binds to its cognate receptor and activates a specific STAT molecule, which then induces a particular set of target genes. Some of the target genes encode SOCS proteins, which exert a negative feedback regulation on the signals from the receptors. (B) Altered STAT signaling networks upon deletion of one family member. If one of the STAT family members is missing, inappropriate activation through binding of other family members to the receptor sites previously occupied by the original member may occur. This will induce a different set of target genes. In addition, reduced expression of SOCS proteins will lead to enhanced activation of signals from other receptors and contribute to a change in the cell’s response. In the case of a loss of STAT5, both GH and PRL are able to activate STAT1 and STAT3, which results in the induction of respective target genes. Loss of STAT5 also results in reduced expression of its prominent target genes Socs2 and Socs3 and, as a consequence, the impaired negative feedback loops will further enhance STAT3 activation.