Cytokine receptor signaling mechanisms.

Recent studies have dramatically advanced our understanding of the post-receptor signaling machinery engaged by members of the cytokine receptor superfamily. Proximal components of this signaling machinery are members of a novel class of protein tyrosine kinases termed JAKs. A working model proposes that ligand-induced dimerization of cytokine receptor subunits triggers the catalytic activation of the associated JAKs, which then couple the receptor to downstream signaling pathways. Ongoing research efforts are also yielding information regarding two potentially interactive pathways of nuclear signaling activated by cytokine receptor occupancy. These pathways are initiated by the activation of the Ras to mitogen-activated protein (MAP) kinase cascade and by the tyrosine phosphorylation of a newly defined set of transcription factors, the signal transducers and activators of transcription (STATs). Collectively, these results begin to provide a molecular basis for the long-observed phenomena of cytokine pleiotropy and redundancy.