MAP kinase links the fertilization signal transduction pathway to the G1/S-phase transition in starfish eggs.
The mechanism by which fertilization initiates S-phase in the zygote is examined by manipulating the activity of MAP kinase in mature starfish eggs. These unfertilized eggs, which are arrested at G1-phase after the completion of meiosis, have high MAP kinase activity but undetectable cdc2 kinase activity. Either fertilization or inhibition of protein synthesis causes a decrease in MAP kinase activity, which is followed by DNA synthesis. Inactivation of MAP kinase with its specific phosphatase, CL100, initiates DNA synthesis in the absence of fertilization, while constitutive activation of MAP kinase with MEK represses the initiation of DNA synthesis following fertilization. Thus, in unfertilized mature starfish eggs, a capacity for DNA replication is already acquired, but entry into S-phase is negatively regulated by MAP kinase activity that is supported by a continuously synthesized protein(s) but not by cdc2 kinase. Upon fertilization, downregulation of MAP kinase activity is necessary and sufficient for triggering the G1/S-phase transition.
Tachibana
K
K
Laboratory of Cell and Developmental Biology, Faculty of Biosciences and Biotechnology, Tokyo Institute of Technology, Midoriku, Yokohama, Japan.
Machida
T
T
Nomura
Y
Y
Kishimoto
T
T
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018797:Cell Cycle Proteins; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation; D005306:Fertilization / Q000502:physiology*; D016193:G1 Phase; D017874:Immediate-Early Proteins / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D008540:Meiosis; D020929:Mitogen-Activated Protein Kinase Kinases; D008954:Models, Biological; D010063:Ovum / Q000201:enzymology / Q000502:physiology*; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011691:Puromycin / Q000494:pharmacology; D016196:S Phase; D015398:Signal Transduction / Q000502:physiology*; D013215:Starfish
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D011500:Protein Synthesis Inhibitors; D011691:Puromycin; C008407:1-methyladenine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases; D001973:Bromodeoxyuridine; D000225:Adenine