The overlapping functions of cytokines largely reflect the properties of the cell surface receptors to which they bind. All cytokine receptors function as multiprotein complexes made up of two or more integral membrane polypeptides, called subunits (Figure 1 bellow). A typical subunit polypeptide has an extracellular domain that participates in cytokine binding, a transmembrane region, and an intracellular domain (also called a cytoplasmic tail gp41) involved in signal transduction the molecular events that transmit signals to the cell interior and induce specific cellular responses when the receptor binds its appropriate cytokine ligand. Some receptors (eg, EPO-R) function as homodimers of a single type of subunit; others (eg, GM-CSFR) function as heterodimers, and still others (eg, IL-2R) as heterotrimers. (more…)

Perhaps the most exciting recent advance in the cytokine signaling field has been the elucidation of the Jak/Stat pathway. The Janus kinase (Jak) family consists of four known enzymes (Jak1, Jak2, Jak3, and Tyk2), each of which associates specifically with the cytoplasmic tails of one or more cytokine receptor subunits. For example, IL-2R associates with both Jak1 and Jak3, which bind its α and γ subunits, respectively. Cytokine binding brings the receptor subunits together and allows the associated Jak proteins to phosphorylate and activate one another. The primary substrates of the activated Jaks are a family of transcription factors called the Stat (for signal transducers and activators of transcription) proteins. The Stat proteins contain SH2 domains and so are recruited to the vicinity of an activated receptor when its kinases become active. (more…)