INTERLEUKIN-2-INDUCED TYROSINE PHOSPHORYLATION OF SHC PROTEINS CORRELATES WITH FACTOR-DEPENDENT T-CELL PROLIFERATION

Interleukin-2 (IL-2) is a growth factor involved in the clonal expansi on of antigen-activated T lymphocytes. Interaction of IL-2 with its re ceptor triggers tyrosine phosphorylation of a series of proteins and r esults in the activation of p21(ras). We report here that Shc, an SH2- containing adaptor protein, is tyrosine-phosphorylated following IL-2 stimulation, IL-2-induced tyrosine phosphorylation of She was detectab le within seconds following IL-2 addition, reaching its highest level by 15 min. Tyrosine phosphorylation of Shc was induced in multiple IL- 2-dependent T cell lines and was found to correlate with IL-2-dependen t cell proliferation. Tyrosine-phosphorylated She was found to be capa ble of associating with the SE2 domain of Grb2 following IL-2 stimulat ion. These results indicate that tyrosine phosphorylation of She and i ts association with Grb2 may be important events in IL-2-initiated sig nal transduction events in T cells.