Kroll S D, Omri G, Landau E M, Iyengar R
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY 10029.
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5182-6. doi: 10.1073/pnas.88.12.5182.
The capability of various activated guanine nucleotide binding regulatory protein (G protein) alpha subunits to induce meiotic maturation was studied. Activated Go 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.
研究了各种活化的鸟嘌呤核苷酸结合调节蛋白（G蛋白）α亚基诱导减数分裂成熟的能力。活化的Go蛋白α亚基（αo*）而非三种抑制性G蛋白α亚基可触发非洲爪蟾卵母细胞的减数分裂成熟。该效应呈浓度依赖性，在100 - 200 pM范围内达到半数最大效应。注射αo可刺激蛋白激酶C活性。共同注射含有蛋白激酶C第19 - 36位残基的肽[PKC-(19 - 36)]（一种特异性蛋白激酶C抑制剂）可阻断αo诱导而非孕酮诱导的成熟。放线菌酮以及注射针对c-mos转录本的反义寡核苷酸可阻断αo诱导的成熟。用mos蛋白特异性单克隆抗体进行免疫沉淀显示，注射αo的卵母细胞中mos蛋白发生了磷酸化。当PKC-(19 - 36)与αo共同注射时，未观察到磷酸化的mos蛋白。这些观察结果表明，αo可通过蛋白激酶C和c-mos的翻译触发非洲爪蟾卵母细胞的减数分裂。我们的结果提出了一种可能性，即通过细胞原癌基因持续活化的G蛋白可能调节细胞周期的恢复。
