Signal transduction cytokines

Rubinstein, M. et al., Recent advances in cytokines, cytokine receptors and signal transduction, Cytokine Growth Factor Rev., 9, 175, 1998. 

Jung, H. W. Chung, Y. S. Kim, Y. S. Park, Y.-K. Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-kB in LPS-stimulated BV-2 microglial cells. Exp. Mol. Med. 2007, 39, 715-721. 

Some cytokine receptors are composed of a single transmembrane polypeptide (e.g. receptors for IL-8, -9 and -10). Many contain two polypeptide components (including the IL-3, -4, and -5 receptors), and a few contain three or more polypeptide components (e.g. the IL-2 receptor contains three polypeptide chains). In some instances a single cytokine may be capable of initiating signal transduction by binding two or more distinct receptors (e.g. IL-1 has two distinct receptors (types I and II), both of which are transmembrane glycoproteins). 

Figure 8.1 Cytokine receptors usually display a unique cytokine ( ligand )-binding domain, but they share additional receptor components that are normally responsible for signal transduction. This explains the molecular basis of pleiotropy. IL-6, IL-11 and LIF receptors, for example, are all composed of a distinct ligand-specific binding domain and a separate subunit (gp 130). gp 130 is responsible for initiating signal transduction and is identical in all three receptors. This is depicted schematically above...

Some cytokine receptors can directly initiate signal transduction upon binding of ligand. In other cases additional elements are involved. For many receptors, the exact intracellular events triggered upon ligand binding remain to be elucidated. However, the molecular details of signal transduction pathways for others (e.g. the interferons) are now understood... 

The intracellular events triggered upon binding of type I or II interferons to their respective receptors are quite similar. The sequence of events, known as the JAK-STAT pathway, has been elucidated over the last few years. It has quickly become apparent that this pathway plays a prominent role in mediating signal transduction, not only for interferon, but also of many cytokines. 

Hideshima, T., Podar, K., Chauhan, D., and Anderson K. 2005. Cytokines and signal transduction. Best Practice and Research Clinical Haematology 18(4), 509-524. 

Martin, M. and Falk, W. 1997. The interleukin-1 receptor complex and interleukin-1 signal transduction. European Cytokine Network 8(1), 5-17. 

The EPO receptor is a member of the haemopoietic cytokine receptor superfamily. Its intracellular domain displays no known catalytic activity, but it appears to couple directly to the JAK2 kinase (Chapter 8) that likely promotes the early events of EPO signal transduction. Other studies have implicated additional possible signalling mechanisms, including the involvement of G proteins, protein kinase C and Ca2+. The exact molecular events underlining EPO signal transduction remain to be elucidated in detail. 

Watowich, S.S., Wu, H., Socolovsky, M., Klingmuller, U., Constantinescu, S.N., andLodish, H.F. 1996. Cytokine receptor signal transduction and the control of haematopoietic cell development. Annual Review of Cell and Developmental Biology 12, 91-128. 

Endocytosis / Phagocytosis Active Transport Cellular Proliferation Intracellular Cytokine Production Intracellular Signal Transduction Intracellular Free Ions (e.g., Na, K, Ca)... 

Eukaryotic ABC transport system Phosphotransferase system (PTS) Ion-coupled transport system Signal Transduction Two-component system Bacterial chemotaxis MAPK signaling pathway Second messenger signaling pathway Ligand-Receptor Interaction G-protein-coupled receptors Ion-channel-linked receptors Cytokine receptors Molecular Assembly Ribosome assembly Flagellar assembly Enzyme assembly... 

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