Cytokine and chemokine receptors

All types of glial cells express various combinations of cytokine and chemokine receptors, which in general control their proliferation, growth and metabolism. These receptors are involved in numerous pathological reactions of glial cells.

The cytokine receptors are represented by two types, type I and type II receptors, which are activated by interferons and interleukins (IL-2, 4, 6, 10, 12, 15 and 21). The signalling pathways triggered by activation of these receptors involve the Janus kinases (JAKs), which in turn control numerous secondary signal transduction proteins, such as for example Signal Transducers and Activators of Transcription (STATs). The latter, after being phosphorylated by JAKs, translocate into the

Cytokine receptors

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Cytokine /

Schwann Cells Ctokines

Figure 5.6 Cytokine receptors - there are many, but the most common are associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Binding of cytokines to the receptor initiates receptor oligomerization and phosphorylation by closely associated JAKs. The phosphorylated receptor becomes a docking site for STAT proteins, which are also phosphorylated by JAKs. Phosphorylated STATs dissociate from the receptors, dimerize and are translocated to the nucleus, where they interact with DNA, hence regulating transcription of genes. (Adapted from Wessman DR, Benveniste EN (2005) Cytokine and chemokine receptors and signaling, In: Neuroglia, Kettenmann H & Ransom BR, Eds, OUP, p. 146-162)

Figure 5.6 Cytokine receptors - there are many, but the most common are associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Binding of cytokines to the receptor initiates receptor oligomerization and phosphorylation by closely associated JAKs. The phosphorylated receptor becomes a docking site for STAT proteins, which are also phosphorylated by JAKs. Phosphorylated STATs dissociate from the receptors, dimerize and are translocated to the nucleus, where they interact with DNA, hence regulating transcription of genes. (Adapted from Wessman DR, Benveniste EN (2005) Cytokine and chemokine receptors and signaling, In: Neuroglia, Kettenmann H & Ransom BR, Eds, OUP, p. 146-162)

nucleus where they initiate transcriptions of various genes, generally known as cytokine responsive genes (Figure 5.6).

The second main signalling pathway controlled by cytokines is represented by tumour necrosis factor (TNF) receptors of the TNFRI and TNFRII families present in all types of glial cells. Activation of TNF receptors regulates activity of JAKs and also utilizes the activation of intracellular transcription factor NF-kB.

Glial cells also express a variety of chemokine receptors. The chemokines are small signalling molecules (8-14 kDa), which regulate cell migration. Chemokine receptors (designated as CCR1-9 and CXCRs) belong to classic seven-transmembrane-domain metabotropic receptors coupled with G-proteins, which in turn, control activation of PLC and phosphatidylinositol-3-OH-kinase (PI3K). Further signalling proceeds through either InsP3, which activates Ca2+ release from the ER, or through DAG, which activates protein kinase C (PKC). Activation of chemokine receptors may also activate JAK/STAT and NF-kB pathways. Chemokine receptors are abundantly expressed in microglia, and they are involved in their activation.

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