PERTUSSIS TOXIN INHIBITS EGF-STIMULATED, PHORBOL ESTER-STIMULATED AND INSULIN-STIMULATED DNA-SYNTHESIS IN BALB/C3T3 CELLS - EVIDENCE FOR POST-RECEPTOR ACTIVATION OF GI-ALPHA

The contribution of the GTP-binding protein, Gi, to EGF, phorbol dibutyrate (PdBu)-, and insulin-stimulated DNA synthesis was examined in BALB c3T3 cells. Pertussis toxin inhibited DNA synthesis by each agonist, particularly at suboptimal agonist concentrations, but the inhibition could be partially overcome with higher agonist concentrations and combinations of these agonists. This suggested that (1) some, but not all, of the mitogenic signals for all three agonists were transduced by Gi (2) Gi may be activated by post-receptor mechanisms involving protein kinase C. Giα-specific antibodies and ADP-ribosylation by pertussis toxin using 32P-NAD each labelled a single protein band, representing one or more species of Giα. Pertussis toxin treatment increased the synthesis of Giα. These results are discussed in relation to possible direct effects of Giα on nuclear control during division. © 1990.