ACTIVATED ALPHA-SUBUNIT OF GO PROTEIN INDUCES OOCYTE MATURATION

The capability of various activated guanine nucleotide binding regulatory protein (G protein) alpha-subunits to induce meiotic maturation was studied. Activated G(o) protein alpha-subunit (alpha-o*) but not the three inhibitory G protein alpha-subunits triggered meiotic maturation in Xenopus oocytes. The effect was concentration dependent with a half-maximal effect in the 100-200 pM range. Injection of alpha-o* stimulated protein kinase C activity. Coinjection of the peptide containing residues 19-36 of protein kinase C [PKC-(19-36)], a specific protein kinase C inhibitor, blocked the alpha-o*- but not progesterone-induced maturation. Cycloheximide and the injection of antisense oligonucleotides specific to the c-mos transcript blocked alpha-o-induced maturation. Immunoprecipitation with a mos protein-specific monoclonal antibody showed that alpha-o-injected oocytes had phosphorylated mos protein. When PKC-(19-36) was coinjected with alpha-o*, phosphorylated mos protein was not observed. These observations indicate that alpha-o*, through protein kinase C and the translation of c-mos, can trigger meiotic division of Xenopus oocytes. Our results raise the possibility that persistently activated G proteins through cellular protooncogenes may regulate cell-cycle resumption.