General Mechanisms of Cytokine Receptor Signaling

Abstract

Cytokines and their receptors constitute a powerful control network, by which various cellular systems in the body signal and coordinate with each other. This chapter focuses primarily on the large cytokine family that activates the shared signal transducer gpl30 to illustrate each point, and then discusses examples from other cytokine families for comparison. Formation of the fully functional cytokine receptor complex involves the interaction of the cytokine with multiple receptor components. Subsequent experiments have shown that all cytokine receptor β components bind to members of the Janus kinase (Jak) family of protein tyrosine kinases. The structure of the four Jak family members is discussed. Finally, the role of phosphatases in regulating cytokine signaling is discussed, as well as the functions of several new signaling molecules are described. Many of the insights into the mechanism of cytokine signaling have created new prospects for creating novel therapeutics. The identification of multiple sites within a single cytokine that interact with different receptor components has allowed the engineering of cytokine muteins that bind tightly to one or two receptor components, but cannot complete receptor complex formation and thus act as antagonists.