Increased cyclic AMP levels block interleukin 2-induced protein kinase C substrate phosphorylation but not the mitogenic response

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Abstract
Protein kinase C (PKC) has been implicated in the signaling of a number of cellular responses including activation of T cells. In the present report we have evaluated the effect of increased cAMP levels on PKC activation after stimulation of two distinct receptor systems on normal human T cells. PKC substrate phosphorylation can be induced via either the CD3 complex or, to a limited extent, the high affinity interleukin 2 (IL2) receptor. Substrate phosphorylation via both pathways is shown to be blocked by increased intracellular levels of cAMP. In accordance with previous reports, the CD3-dependent autocrine proliferative response could also be blocked by a cAMP-dependent mechanism. Since direct activation of PKC with a phorbol ester reversed this inhibition, a causal relationship between cAMP-dependent PKC blockage and inhibition of the CD3 response is suggested. In contrast, however, initiation of IL2-induced proliferation was essentially unaltered by cAMP and could progress in the apparent absence of PKC activity. Thus, this study indicates that IL2-induced proliferation can under such conditions be completely uncoupled from IL2-induced PKC activation in normal T cells.
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