Effects of pertussis toxin on the erythropoietin-stimulated proliferation and differentiation of erythroid-responsive cells.

Erythropoietin (Ep) stimulates the proliferation and differentiation of erythroid progenitor cells. We have investigated the possibility that guanyl nucleotide regulatory (G) proteins may be involved in Ep signal transduction. Pertussis toxin (PT) was found to inhibit Ep-stimulated [3H]-thymidine incorporation and large erythroid colony formation in a dose-dependent fashion, but had no effect on small colony formation or on Ep-induced differentiation. PT specifically adenosine diphosphate-ribosylated a major protein with an apparent molecular mass of 41 kD in erythroid progenitor cell membranes. These findings indicate that the transduction of the Ep signal for proliferation could be mediated in the early steps by a PT-sensitive G protein.