ABSTRACT
Cytokines play roles of regulating cell proliferation, differentiation, and cell death. A
cytokine exhibits diverse functions in various cell types. On the other hand, different cytokines often display the similar effect on the same target. These functional pleiotrophy and redundancy are characteristic features of cytokines and the molecular mechanisms of these features could be understood by the clarification of signal transduction through cytokine receptors (1). Signals of all the cytokines are transmitted to the inside of cells through their receptor on the cell surface. Molecular cloning of cytokine receptors have revealed that they are classified to several groups. Receptors for growth factors such as PDGF, EGF, and FGF, and CSF-1 have a tyrosine kinase domain in their cytoplasmic regions. Receptors for TGF-β-type cytokines such as BMP and activin have a serine/threonine kinase domain in the cytoplasmic region. While, receptors for α-helical cytokines such as interleukins (IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-11, IL-12, IL15, etc.), colony stimulating factors (G-CSF, GM-CSF, erythropoietin, etc.), interferons, and hormones (growth hormone, prolactin, leptin, etc.) do not have any endogenous catalytic activities. These receptors have structural similarities in both the extracellular and cytoplasmic regions, thus they are defined as members of the type I cytokine receptor superfamily or hematopoietin receptor superfamily (2,3). Signaling through the type I cytokine receptors is governed by a similar set of signal transducing molecules, in particular, Janus kinases (JAKs) and signal transducer and activator of transcriptions (STATs) (4-8). We focus this review on the signaling through the type I cytokine receptor.
