Extensive studies on the IL-2 and IL-2 receptor system have established fundamental principles of immune responses and signal transducing mechanisms of hematopoietic cell proliferation and survival. IL-2Rb and IL-2Rg chains are associated with multiple tyrosine kinases including JAK1, JAK3 and other tyrosine kinases such a p56lck. IL-2 binding to these receptors leads to conformational changes of the receptors followed by the recruitment of several kinases leading to their activation. The JAKs and activated tyrosine kinases appear to be a trigger for the downstream signal cascades. Other downstream messenger molecules such as the STATs, Shc, PI3K-Akt, Ras-ERK1/2 and so on, cross talk with this cascades. The interplay however leading to the regulation of target genes still remain largely obscure. For example, although phosphorylation of tyrosine 338 of IL-2Rb is required for both signal transduction to Shc and PI3K, how it regulates further signals from Shc to the Grb2-Sos-Ras pathway or to the PI3K-Akt pathway is unknown. There are also conflicting reports on the functional roles of STAT5, STAT1 and STAT3 on IL-2 signaling. Further work is needed to clarify how the multiple kinases trigger multiple signaling cascades and cooperate with each other in the regulation of gene induction for cell growth, survival or differentiation in different cell types and conditions in vitro and also in vivo. Key words : IL-2, tyrosine kinase, signal transduction, cytokin
