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1 Postępy Higieny i Medycyny Doświadczalnej

1 2002

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Contribution of interleukin 2 and interleukin 12 receptors in signal transduction

100%

Lyszkiewicz M. , Pajtasz-Piasecka E.

nr 6

707-731

Interleukin 2 (IL-2) and interleukin 12 (IL-12) belong to lympho-hematopoietic cytokines and play a critical role in the promotion and enhancement of cellular response. IL-2 as the second signal of antigenic stimulation facilitates the transition of the cell cycle from phase G1 to phase S and is responsible for the regulation of T lymphocytes proliferation and the activation of cytotoxic T cells, natural killers, macrophages and granulocytes. IL-12 is the dominant factor in T helper cells polarization leading to the secretion of IFN-. Receptors for both of the cytokines (IL-2R or IL-12R) represent class I cytokine receptors composed of multiple subunits. Generally, they contain a similar extracellular conserved motif of four cysteines, and amino acid sequence - WSXWS (interacting directly with ligand) but possess no catalytic domens in the intrinsic tail of the chains. For this reason, to transfer the impact, the association with number of signaling molecules, allowing the activation of the signaling pathways is required. The connections of IL-2R or IL-12R with their ligands recruit receptor-associated cytoplasmic proteins from the JAK family (JAK1/JAK3 or JAK2/TYK2, respectively), which catalyze the phosphorylation of themselves and intrinsic tyrosine residues on the receptor, creating STAT docking sites. This phosphorylated and subsequent dimerised proteins bind rapidly to DNA and activate it. This review, presents the differences and similarities between the signaling pathways triggered by IL-2R or IL-12R ligation.