Interleukin-7 induces T cell proliferation in the absence of ErK/MAP kinase activity

Interleukin (IL)-7 and IL-2 are important lymphoproliferative cytokines which both use the gamma c chain as part of their respective receptors. To learn more of their signaling mechanisms a comparison was made of the patterns of intracellular tyrosine phosphorylated proteins induced by these cytokines in the murine T cell line, CT6. Several similarities were revealed in the tyrosine phosphorylated proteins induced. However, a notable subset of proteins of mainly <60 kDa were only phosphorylated by IL-2. Characterization of the two most prominent bands of this subset, pp54 and pp42, revealed these to contain Shc and p42(MAP/Erk) kinase, respectively. Further studies confirmed that IL-7 was unable to induce the phosphorylation of either the p44(MAP/Erk) or p42(MAP/Erk) or activation of the kinases. Shc is involved in activation of p21(ras), a key event in the signaling cascade, via p72(raf) and MEK, leading to MAP/Erk kinase (MAPK) activation. These data indicate that this pathway is not utilized by IL-7 and may not, therefore, be essential for cytokine-driven T cell proliferation. This possibility was supported by studies with the MEK inhibitor PD098059, which had no selective effect on CT6 proliferation induced by IL-2 as compared with IL-7, although the drug completely inhibited MAP/Erk phosphorylation induced by IL-2.