Signal transduction through cytokine receptors. 1998

M Hibi, and T Hirano
Division of Molecular Oncology, Osaka University Medical School, Japan.

Receptors for interleukins, colony stimulating factors, and hormones have a homology in their extracellular regions, characterized by the conserved cysteine residues and the tryptophan-serine-x-tryptophan-serine motif, thus, they are classified to the type 1 cytokine receptor superfamily. Janus tyrosine kinase (JAKs) have been found to be involved in the signal transduction through type I cytokine receptors. JAKs associate with the membrane proximal region in the cytoplasmic domain having box1 and box2, which are conserved among the family, and upon the stimulation JAKs can be aggregated following the receptor dimerization and activated probably by transphosphorylation. JAKs then phosphorylate the receptor and various signal transducing molecules, including STATs (signal transducer and activator of transcriptions) and other SH2-containing adapter molecules. STATs were initially identified as transcription factors containing a SH2 domain and regulating interferons-inducible genes. STATs can be tyrosine phosphorylated by JAKs and form dimer (either hetero- or homo-dimers) to enter the nucleus, resulting in the expression of a set of genes. On the other hand, adapter molecules such as Shc, GRB2, and SHP-2 have been shown to link the cytokine receptors to Ras, followed by the activation of the Raf-MEK-MAP kinase pathway, leading to the activation of various transcription factors in the nucleus. These two signals are generated by different ways upon the stimulation of the receptors and they elicit a variety of biological functions in various cell types. In this review, we will discuss the mechanism by which cytokines activate JAKs, STATs, and a variety of adapter molecules. We further discuss the roles of each signal transduction pathways in the expression of biological activities of cytokines.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D018121 Receptors, Cytokine Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells. Cytokine Receptors,Cytokine Receptor,Receptors, Cytokines,Cytokines Receptors,Receptor, Cytokine

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