Lck is involved in interleukin-2-induced proliferation, but not cell survival, in human T cells through a MAP kinase-independent pathway

The role of Lck in IL-2-induced proliferation and cell survival is still co ntroversial. Here, we show that the Src family kinase inhibitor, PP1, reduc ed the IL-2-induced proliferation of human T cells significantly without in hibiting the anti-apoptotic effect of IL-2. As Lck is the only Src family k inase activated upon IL-2 stimulation in T cells, this indicates that Lck i s involved in IL-2-induced proliferation but not survival. IL-2-induced MAP kinase activation was only slightly inhibited by PP1, suggesting that Lck is not essential for IL-2-induced MAP kinase activation in human T cells, W e found that an IL-2-sensitive, human mycosis fungoides-derived tumor T cel l line is Lck negative, and that the IL-2-induced MAP kinase activation is comparable to non-cancerous T cells, although a little delayed in kinetics, An Lck expressing clone was established by transfecting Lck into mycosis f ungoides tumor T cells, but Lck had no influence on the delayed kinetics of MAP kinase activation, indicating that Lck is not essential for MAP kinase activation in mycosis fungoides tumor T cells or in non-cancerous T cells. Taken together, this indicates that Lck is involved in IL-2-induced prolif eration, but not cell survival, through a pathway not involving MAP kinase.