Signaling domains of the interleukin 2 receptor

Interleukin (IL-)2 and its receptor (IL-2R) constitute one of the most exte nsively studied cytokine receptor systems. IL-2 is produced primarily by ac tivated T cells and is involved in early T cell activation as well as in ma intaining homeostatic immune responses that prevent autoimmunity. This revi ew focuses on molecular signaling pathways triggered by the IL-2/IL-2R comp lex, with an emphasis on how the IL-2R physically translates its interactio n with IL-2 into a coherent biological outcome. The IL-2R is composed of th ree subunits, IL-2R alpha, IL-2R beta and gammac, Although IL-2R alpha is a n important affinity modulator that is essential for proper responses in vi vo, it does not contribute to signaling due a short cytoplasmic tail. In co ntrast, IL-2R beta and gammac together are necessary and sufficient for eff ective signal transduction, and they serve physically to connect the recept or complex to cytoplasmic signaling intermediates. Despite an absolute requ irement for gammac in signaling, the majority of known pathways physically link to the receptor via IL-2R beta, generally through phosphorylated cytop lasmic tyrosine residues. This review highlights work performed both in cul tured cells and in vivo that defines the functional contributions of specif ic receptor subdomains-and, by inference, the specific signaling pathways t hat they activate-to IL-2-dependent biological activities. (C) 2001 Academi c Press.