Cell cycle and growth factor-dependent phosphoprotein of 78kD differently regulated in normal and transformed mouse fibroblasts.

A novel 78kD phosphoprotein (pp78) of BALB/c 3T3 mouse fibroblasts is reported. Its properties of appearance in late G1 phase, dependence on specific growth factors, and altered constitutive kinetics in benzo(a)pyrene-transformed (BPA31) cells suggest its role in growth and transformation. Pp78 phosphorylation is in a dynamic state and is stabilized by inhibitors of protein and mRNA synthesis, possibly because of inhibition of a labile phosphatase or protease. Its disappearance in S phase and its low level in exponential cells also indicate a dynamic control that is dependent on growth conditions. Enhancement by phorbol myristate acetate indicates that phosphorylation of pp78 is a consequence of protein kinase C activation, but it appears much later than does an 80kD phosphoprotein (pp80), which is a recognized substrate of kinase C. No simple relation between the appearance of pp78 and mitogenesis was found. Two other phosphoproteins varied with growth conditions. One is the pp80 kinase C substrate which was found in the untransformed (A31) 3T3 cells early after stimulation but was absent in BPA31 cells. The other is an 18kD phosphoprotein that appeared shortly after quiescent 3T3 cells were stimulated.