Signal transduction pathways that contribute to CDK1/cyclin B activation during the first mitotic division in sea urchin embryos.
In sea urchins, fertilization triggers a rapid rise in protein synthesis necessary for activation of CDK1/cyclin B, the universal cell cycle regulator. It has been shown that FRAP/mTOR is required for eIF4E release from the translational repressor 4E-BP, a process that occurs upstream of de novo cyclin B synthesis. Here, we investigate whether PI 3-kinase acts independently or upstream from FRAP/mTOR in the signal transduction pathway that links fertilization to the activation of the CDK1/cyclin B complex in sea urchin egg. We found that wortmannin, a potent inhibitor of PI 3-kinase, partially inhibited the global increase in protein synthesis triggered by fertilization. Furthermore, wortmannin treatment induced partial inhibition of cyclin B translation triggered by fertilization, in correlation with an intermediate effect of the drug on 4E-BP degradation and on the dissociation of the 4E-BP/eIF4E complex induced by fertilization. Our results presented here suggest that PI 3-kinase activity is required for completion of mitotic divisions of the sea urchin embryo. Incubation of eggs with wortmannin or microinjection of wortmannin or LY 294002 affects drastically mitotic divisions induced by fertilization. In addition, we found that wortmannin treatment inhibits dephosphorylation of the tyrosine inhibitory site of CDK1. Taken together, these data suggest that PI 3-kinase acts upstream of at least two independent targets that function in the CDK1/cyclin B activation triggered by fertilization of sea urchin oocytes. We discuss the significance of these results concerning the cascade of reactions that impinge upon the activation of the CDK1/cyclin B complex that follows sea urchin oocyte fertilization.
Salaün
Patrick
P
Station Biologique de Roscoff, Université Pierre et Marie Curie (EI 37), Centre National de la Recherche Scientifique (CNRS, FRE 2775), Institut National des Sciences de l'Univers (INSU). BP 74, 29682 Roscoff, France.
Le Breton
Magali
M
Morales
Julia
J
Bellé
Robert
R
Boulben
Sandrine
S
Mulner-Lorillon
Odile
O
Cormier
Patrick
P
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology*; D005306:Fertilization; D008938:Mitosis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012617:Sea Urchins; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins / Q000378:metabolism
D016203:CDC2 Protein Kinase; D019926:Cyclin B; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins