Signaling mechanisms of cytokine receptors and their perturbances in disease

Cytokines regulate the proliferation and differentiation of cells through t heir interaction with specific receptors on the surface of target cells whi ch are coupled to intracellular signal transduction pathways. The cytokine receptor class I superfamily, characterized by structural homology in the e xtracellular domain, includes receptors for many interleukins and hematopoi etic growth factors, but also those of growth hormone, leptin, ciliary neur otrophic factor (CNTF), oncostatin M (OSM), leukemia inhibitory factor (LIF ) and cardiotrophin-1 (CT-1). The receptors for interferons are structurall y distinct and have therefore been categorized separately (class II cytokin e receptors). The discovery of the JAK/STAT pathway in the early 1990s has been an important step forward in deciphering cytokine mediated signaling. This pathway connects activation of the receptor complexes directly to tran scription of genes. Studies of humans and mice, deficient for one of the JA Ks or STATs, have revealed crucial roles of these molecules in embryonic de velopment, blood cell formation and immune responses. In addition, recent s tudies have revealed some of the mechanisms that control the activation of the JAKs and STATs, which contribute to signal intensity and specificity. I n this review we will summarize these recent insights and discuss their imp lications for a variety of pathological conditions. (C) 2000 Elsevier Scien ce Ireland Ltd. All rights reserved.