Hematopoietic cytokines, cytokine signaling

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... 

Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Silvennoinen O. Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol 1995 13 369-398. 

Fig. 1. Grouping of hematopoietic cytokine receptors by shared receptor usage. The majority of the hematopoietic cytokine receptors incorporate one of three shared signaling receptors, either the common beta (/ c) chain, the common gamma (7,-) chain or gplSO. The crystal structure of the growth hormone (red) complex (inset) was the first structure of a four helix bundle cytokine in complex with its receptor (green) (de Vos et al, 1992) and established the paradigm of cytokine/receptor complex formation. (See Color Insert.)...

The receptor for CNTF has recently been cloned (Davis et al., 1991) and appears to be exclusively expressed in the nervous system and in skeletal muscle. In contrast to other known receptors, the receptor for CNTF is anchored to the plasma membrane by a glycosyl-phospha-tidylinositol linkage (Davis et al., 1991). Its primary structure is most similar to the IL-6 receptor. Furthermore, both CNTF and the structurally related leukemia-inhibitory factor (see above) use the IL-6 signal transducer gpl30 (Ip et al., 1992). These observations raise the possibility that the receptors for CNTF, leukemia-inhibitory factor and hematopoietic cytokines are able to interact with each other and to activate related signaling pathways in diverse cell types (Bazan, 1991 Davis and Yancopoulos, 1993). It has been shown by Lillien et al. (1990) that some biological functions of CNTF, e.g. induction of type-2 astrocyte development, require cooperation with as yet unknown ECM-associated molecule(s). 

Erythropoietin (EPO), a hematopoietic cytokine, is a glycoprotein that mediates cytoprotection in brain and spinal cord through activation of multiple signaling pathways (Grasso et al., 2006). In addition, EPO also has a crucial hormonal role in red... 

In vitro and in vivo studies have shown that stromal cells provide a rich environment of signals (cytokines, extracellular matrix, adhesion molecules etc.) that control proliferation, survival and differentiation of hematopoietic progenitor cells (Chailakhian, 1978 Verfaillie, 2002). Recently investigators incorporated stromal components into the expansion cultures (Rawano et al. 

IL-4 mediates its effects via specific IL-4 receptors that are expressed on a number of tissues including hematopoietic cells, endothelium, hepatocytes, epithelial cells, fibroblasts, neurons and muscles. The receptor is composed of an a chain, which is the high-affinity receptor, but its signaling requires a second chain, a y chain (yC), which is also a component of IL-2 receptors. However, the presence of a y chain does not significantly increase the affinity of the receptor complex for IL-4. IL-4 causes the heterodimerization of the a chain with the y chain, resulting in IL-4 receptor-dependent signaling pathway. As is the case with other cytokines,... 

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