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. 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-gamma-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.
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006147:Guanine / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D009173:Mycophenolic Acid / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D013873:Thionucleotides / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D013873:Thionucleotides; D003208:Concanavalin A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006147:Guanine; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D009955:Ornithine Decarboxylase; D009173:Mycophenolic Acid