Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) stimulates Src family kinases, tyrosine phosphorylation of several proteins, conversion of Ras to its active GTP-bound form, and eventually c-fos, c-jun, and c-myc induction. The IL-2Rβ chain plays a crucial role in IL-2R signaling. Within the cytoplasmic domain of the β chain, a region essential for mitogenesis and another involved in binding the Src family kinase Lck have been defined. The β chain itself is tyrosine-phosphorylated upon IL-2 stimulation. Since the adapter protein Shc acts upstream of Ras and is involved in T cell receptor-mediated Ras activation, we examined the role of Shc in IL-2 signaling. Shc was found to be tyrosine-phosphorylated upon IL-2 stimulation in CTLL-20 cells. After its phosphorylation, Shc interacted with another adapter protein, Grb2, and, via Grb2, with the Ras GTP/GDP exchange factor mSOS. After IL-2 stimulation, Shc also associated with the IL-2Rβ chain. Thus, during IL-2 signaling, the interaction of Shc with the IL-2Rβ chain and its simultaneous association with Grb2 and mSOS may couple IL-2R stimulation to Ras signaling.
|Number of pages||4|
|Journal||Journal of Biological Chemistry|
|State||Published - 1994|