Mustelin T, Pösö H, Andersson L C
EMBO J. 1986 Dec 1;5(12):3287-90. doi: 10.1002/j.1460-2075.1986.tb04641.x.
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.
鸟氨酸脱羧酶的快速激活是人类T淋巴细胞诱导有丝分裂反应过程中最早被认识到的事件之一。在此我们表明，通过瞬时膜通透技术引入人类T细胞的不可水解的GTP类似物鸟嘌呤-5-(γ-硫代)三磷酸和鸟苷-5-亚氨基二磷酸，在诱导早期鸟氨酸脱羧酶活性方面，可以替代外部有丝分裂配体，如伴刀豆球蛋白A。新霉素在已知与磷酸肌醇结合的浓度下抑制这种快速激活。多磷酸肌醇分解形成的两种化合物之一，肌醇-1,4,5-三磷酸，也诱导鸟氨酸脱羧酶活性。另一种，二酰基甘油，显然不会，因为被认为模拟二酰基甘油作用的佛波酯，十四酰佛波醇乙酸酯，在给药后数小时内不会改变T细胞中的基础鸟氨酸脱羧酶活性。这些发现表明鸟嘌呤核苷酸结合调节（G-）蛋白参与有丝分裂信号的转导。这种G蛋白的细胞内靶系统可能包括磷酸肌醇分解和肌醇三磷酸的生成，这可能参与鸟氨酸脱羧酶的早期激活。
