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

Abstract

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. One of the two compounds formed in polyphosphoinositide breakdown, inositol-1,4,5-trisphosphate, also induces ornithine decarboxylase activity. The other, diacylglycerol, apparently does not, since the phorbol ester, tetradecanoyl phorbol acetate, which is thought to mimic the action of diacylglycerols, does not alter basal ornithine decarboxylase activity in T cells until several hours after administration. These findings indicate that guanine nucleotide-binding regulatory (G-) protein(s) participates in the transduction of the mitogenic signal. The intracellular target system for this G-protein may include phosphoinositide breakdown and generation of inositoltrisphosphate, which might be involved in the early activation of ornithine decarboxylase.