Maturation-promoting factor and the regulation of the cell cycle

Maturation-promoting factor (MPF) is a cell cycle control element able to cause metaphase when injected into amphibian oocytes or when incubated with nuclei in a cell-free system. Highly purified MPF consists of a complex between a 34K (K = 10(3) Mr) serine/threonine protein kinase, identified as a Xenopus homolog of the cdc2+ gene product, p34cdc2, and a 45K substrate, identified as a Xenopus B-type cyclin. p34cdc2 is also present in purified preparations of chromatin-derived growth-associated histone H1 kinase from Novikoff hepatoma cells. p34cdc2 is active when dephosphorylated and inactive when phosphorylated during oocyte meiotic cell cycles and in mitotic cell cycles following egg activation. Analysis of the substrate specificity of p34cdc2 indicates a consensus sequence for phosphorylation of (K/R)S/TP(X)K/R. Among substrates identified with this consensus are histone H1 and the pp60c-src proto-oncogene, which is known to be activated and phophorylated in mitosis. MPF injection into oocytes activates ribosomal protein S6 kinase II, which is also a lamin kinase. The mechanism of activation is indirect, possibly involving the c-src proto-oncogene. Continued analysis of regulation of MPF activation/inactivation and characterization of substrates for phosphorylation will have important implications for cell cycle and cell growth control.