Signalling by cytokines interacting with the interleukin-2 receptor gamma chain

The interleukin-2 (IL-2) receptor gamma chain (gamma c) is shared by recept or complexes used by IL-2, IL-4, IL-7, IL-9 and IL-15, all of which are cyt okines involved in lymphocyte development and/or activation. gamma c is phy sically and functionally associated with the JAK3 tyrosine kinase. This mol ecular pair may be considered as the trigger of the signalling cascades, in ducing the activation of JAK1 upon heterodimerization with a cytokine-speci fic receptor component. JAK1, JAK3 and other tyrosine kinases, the nature o f which varies between cytokines, phosphorylate the receptor, thereby creat ing docking sites for signalling molecules. Among them, PI 3-kinase and dow nstream effectors play a central role in the signalling processes involved in proliferation and inhibition of apoptosis for every gamma c-interacting cytokine, although the mechanism of activation may vary between cytokines. Other important mediators - STAT transcription factors - regulate the expre ssion of specific genes. IL-2, IL-7, IL-9 and IL-15 activate STAT3 and STAT 5, in contrast to IL-4, which activates STAT6. These cytokines also trigger specific pathways, such as the MAP kinase cascade for IL-2 and IL-15, and the cascade responsible for immunoglobulin gene V-D-J rearrangement in resp onse to IL-7.