Growth signal transduction: rapid activation of covalently bound ornithine decarboxylase during phosphatidylinositol breakdown.

We have previously shown that treatment of T lymphocytes with mitogenic ligands induces a rapid activation of ornithine decarboxylase (ODC) through a mechanism that is independent of protein synthesis but requires energy and an intact cytoskeleton. Here we show by immunoprecipitation experiments and by chemical analyses that ODC is covalently linked to the cell membrane by inositol. Treatment of sonicated cells with a phosphatidylinositol-specific phospholipase C from B.

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

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.

Role of G-proteins in T cell activation: non-hydrolysable GTP analogues induce early ornithine decarboxylase activity in human T lymphocytes.

Rapid activation of ornithine decarboxylase is one of the earliest recognized events during induction of a mitogenic response in human T lymphocytes. Here we show that the non-hydrolysable GTP analogues guanine-5-(gamma-thio)trisphosphate and guanylyl-5-imidodiphosphate, introduced into human T cells by means of a transient membrane permeabilization technique, can replace an external mitogenic ligand, such as concanavalin A, in inducing early ornithine decarboxylase activity. Neomycin inhibits this rapid activation at concentrations known to bind to phosphoinositides.

myo-Inositol reverses Li+-induced inhibition of phosphoinositide turnover and ornithine decarboxylase induction during early lymphocyte activation.

One of the earliest detectable responses by T lymphocytes in vitro to various mitogenic ligands is the rapid induction of ornithine decarboxylase (ODC) activity (Scott et al., Eur. J.