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, expressing 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 necessary for IL-2 stimulation of proliferation, as deletion of a region of the cytoplasmic domain of the IL-2 receptor beta chain, essential for 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 proliferation. However, elevation of Erk2 activity was not sufficient to stimulate proliferation, as protein kinase C activation stimulated Erk2 activity but not DNA synthesis. Also, cells exposed to IL-2 in the presence of rapamycin showed full Erk2 activation but not DNA synthesis. These data suggest that IL-2 must stimulate both Erk2 activity and a further pathway(s) to trigger cell proliferation.
Perkins
G R
GR
Chester Beatty Laboratories, Institute of Cancer Research, London, England.
Marvel
J
J
Collins
M K
MK
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1