Cytokine receptor architecture, structure and genetic assembly

In this review major structural and molecular characteristics of interleukin-6-type cytokine receptors consisting of ligand-specific (e.g., IL-6 receptor) and public (gp130) elements are outlined. The peculiar shedding feature of the ligand-binding receptor subunit provides a possibility to form a receptor-ligand complex in the soluble phase, followed by an autocrine or paracrine re-attaching to the membrane bound gp130. This situation provides a dynamic 4-chain model for IL-6-type receptors, depending on a critical balance between membrane bound and soluble cytokine receptors. The generation and transduction of intracellular signal for IL-6-type cytokine receptors based primarily on generation of phospho-tyrosine proteins. In this set of events kinases of the JAK family are basically involved. Although not all primary substrates are uncovered, gp130 and stat proteins are phosphorylated. The variability of the JAK/Stat system and its still not clear relation to the specificity of cytokine actions are discussed.