GTP dependence of the transduction of mitogenic signals through the T3 complex in T lymphocytes indicates the involvement of a G-protein

Abstract

The T3 molecule on the surface membrane of T lymphocytes is involved in the transduction of the proliferation signal generated by an interaction between the antigen receptor and an antigen, to the interior of the T cell. Mitogenic monoclonal antibodies against the T3 molecule and mitogenic lectins induce a rapid (within 5 min) protein synthesis-independent activation of ornithine decarboxylase (ODC) in human T lymphocytes. When T cells are selectively depleted of guanine nucleotides by treatment with mycophenolic acid, the early mitogen-induced activation of ODC is completely inhibited. The inhibition rapidly reverted on the addition of guanine a few minutes before the mitogenic stimulation, and even more rapidly by GTP directly introduced into the T cells by a transient membrane permeabilization. GTP can be substituted for by a non-hydrolyzable GTP analogue, GTP-γ-S, which also induces ODC activity by itself in human T cells. These results suggest that a G-protein(s) is involved in the transduction of the proliferation signal in human T cells.