INTERLEUKIN-2 ACTIVATES EXTRACELLULAR SIGNAL-REGULATED PROTEIN KINASE-2

Interleukin 2 (IL-2) stimulated activation of the 42-kD extracellular signal-regulated kinase 2 (Erk2) in murine IL-3-dependent cells, expre ssing either high or intermediate affinity IL-2 receptors. Activation was both rapid, occurring within 5 min of IL-2 addition, and prolonged , remaining elevated for 30 min. Activation of Erk2 appeared to be nec essary for IL-2 stimulation of proliferation, as deletion of a region of the cytoplasmic domain of the IL-2 receptor beta chain, essential f or IL-2 stimulation of proliferation, abolished Erk2 activation by IL- 2. Furthermore, cells that had been deprived of cytokine for 24 h were then refractory to IL-2 stimulation of both Erk2 activity and prolife ration. However, elevation of Erk2 activity was not sufficient to stim ulate proliferation, as protein kinase C activation stimulated Erk2 ac tivity but not DNA synthesis. Also, cells exposed to IL-2 in the prese nce of rapamycin showed full Erk2 activation but not DNA synthesis. Th ese data suggest that IL-2 must stimulate both Erk2 activity and a fur ther pathway(s) to trigger cell proliferation.