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Cytokines

  • Walter M. Lewko
  • Robert K. Oldham
Chapter

Abstract

Cytokines are regulatory proteins, produced and secreted by various cells, which control immune response, hematopoiesis, inflammation, wound repair, and tissue morphogenesis. Cytokines may be secreted or membrane-bound. Secreted cytokines may act locally as autocrine or paracrine factors or over some distance as would a hormone. Membrane-bound cytokines act by cell—cell contact, communicating information from one cell to another, often bidirectionally. There are cell surface receptors for each cytokine which bind the cytokine specifically. Receptor subunits may be shared between different cytokines. Binding the cytokine brings about signaling and a series of cell-activating events. For many cytokine receptors (not all), this involves increased phosphorylation of certain tyrosine residues on key cellular proteins. Kinases are the enzymes which carry out phosphorylation. Receptors may themselves be kinases which activate upon binding. More typically, the activated receptor may recruit cytosolic kinases, for example, mitogen-activated protein kinase (p38 MAPK)* and Janus kinases, (Jak1, Trk and Jak 3) [89, 463, 484, 875, 1483]. As the kinases bind the receptor complex, their enzymatic activities increase and an array of cellular proteins is phosphorylated, in certain cases including the receptor itself. These modifications bring about changes, increases or decreases, in each protein’s activity. Among these proteins are the STAT proteins which control gene expression. When phosphorylated, STAT proteins translocate from the cytoplasm to the nucleus and bind specific enhancer segments allowing the expression of the genes needed to bring about a cytokine’s response.

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