CYTOKINE RECEPTOR ARCHITECTURE, STRUCTURE AND GENETIC ASSEMBLY

In this review major structural and molecular characteristics of inter leukin-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 pos sibility to form a receptor-ligand complex in the soluble phase, follo wed by an autocrine or paracrine re-attaching to the membrane bound gp 130. This situation provides a dynamic 4-chain model for IL-6-type rec eptors, depending on a critical balance between membrane bound and sol uble cytokine receptors. The generation and transduction of intracellu lar signal for IL-6-type cytokine receptors based primarily on generat ion of phospho-tyrosine proteins. In this set of events kinases of the JAK family are basically involved. Although not all primary substrate s are uncovered, gp130 and stat proteins are phosphorylated. The varia bility of the JAK/Stat system and its still not clear relation to the specificity of cytokine actions are discussed.