Progesterone but not ras requires MPF for in vivo activation of MAPK and S6 KII: MAPK is an essential conexion point of both signaling pathways.
Induction of mitosis in Xenopus laevis oocytes by hormones and the oncogenic ras-p21 protein has been shown to correlate with a cascade of phosphorylations of the Ser/Thr family of kinases. However, the exact hierarchy of enzymes and their mutual interdependency has not been fully elucidated yet. We have used the Xenopus laevis system to investigate the mechanism of activation of the Ser/Thr kinases cascade and their relationship. Comparison between progesterone-induced germinal vesicle breakdown (GVBD), a hallmark of mitosis in oocytes, to that triggered by ras-p21, revealed the existence of at least two independent mechanisms to activate the MAP kinase enzyme in vivo. While progesterone function is dependent of cdc2 protein kinase activity, ras-p21 is independent of this enzyme. However, both progesterone and ras-p21 converge at the MAP kinase level, and depletion of MAP kinase activity inhibits the GVBD and S6 kinase II activation induced by both progesterone and ras-p21. These results provides further evidence that MAP kinase is a critical step for regulation of the cell cycle in oocytes and a critical point where ras and progesterone signaling converge.
Instituto de Investigaciones Biomédicas, CSIC, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
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Carnero
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Jiménez
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JC
Lacal
D015075:2-Aminopurine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D016200:Maturation-Promoting Factor / Q000502:physiology*; D008845:Microinjections; D008938:Mitosis / Q000187:drug effects; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D019893:Ribosomal Protein S6 Kinases; D014982:Xenopus laevis
D015075:2-Aminopurine; D011374:Progesterone; C001020:N(6),N(6)-dimethyladenine; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D016283:Proto-Oncogene Proteins p21(ras); D000225:Adenine