The Negative Regulation of JAK/STAT Signaling

Abstract

Cytokines are a large family of protein messengers, which are classified into four families based on their structures: hematopoietin, interferon, chemokine, and tumor necrosis factor (TNF). These proteins elicit diverse cellular responses upon binding to cognate transmembrane receptors that are expressed on the surface of target cells. Typically, the intracellular portions of hematopoietin receptors lack any intrinsic kinase activity and are therefore dependent on receptor-associated effectors, such as Janus kinases (JAKs), to initiate signaling pathways. Due to the importance of JAK tyrosine phosphorylation for signal transduction, especially within the activation loop, it follows that deph..