Signaling domains of the interleukin 2 receptor.
Interleukin (IL-)2 and its receptor (IL-2R) constitute one of the most extensively studied cytokine receptor systems. IL-2 is produced primarily by activated T cells and is involved in early T cell activation as well as in maintaining homeostatic immune responses that prevent autoimmunity. This review focuses on molecular signaling pathways triggered by the IL-2/IL-2R complex, with an emphasis on how the IL-2R physically translates its interaction with IL-2 into a coherent biological outcome. The IL-2R is composed of three subunits, IL-2Ralpha, IL-2Rbeta and gammac. Although IL-2Ralpha is an important affinity modulator that is essential for proper responses in vivo, it does not contribute to signaling due a short cytoplasmic tail. In contrast, IL-2Rbeta and gammac together are necessary and sufficient for effective signal transduction, and they serve physically to connect the receptor complex to cytoplasmic signaling intermediates. Despite an absolute requirement for gammac in signaling, the majority of known pathways physically link to the receptor via IL-2Rbeta, generally through phosphorylated cytoplasmic tyrosine residues. This review highlights work performed both in cultured cells and in vivo that defines the functional contributions of specific receptor subdomains-and, by inference, the specific signaling pathways that they activate-to IL-2-dependent biological activities.
Gaffen
S L
SL
Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, Buffalo, NY14214, USA. sgaffen@buffalo.edu
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D015375:Receptors, Interleukin-2 / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D007376:Interleukin-2; D021122:Protein Subunits; D015375:Receptors, Interleukin-2