Okadaic acid suppresses calcium regulation of mitosis onset in sea urchin embryos.
We show that a phosphatase inhibitor, okadaic acid, induces premature and persistent mitosis during the first cell cycle in sea urchin embryos. Okadaic acid-induced mitosis requires protein synthesis, suggesting that it activates the protein synthesis-requiring mitotic H1 kinase. By microinjecting the calcium chelators BAPTA and EGTA and by measuring Cai using fura-2, an indicator dye, we show that okadaic acid-induced mitosis is independent of the calcium signal that usually triggers mitosis onset in sea urchin embryos. Disabling the calmodulin kinase II that is thought to respond to the mitotic Cai signal using a peptide inhibitor fails to prevent mitosis in response to okadaic acid. These data suggest that okadaic acid bypasses calcium regulation of mitosis by inducing constitutive phosphorylation of a site on the H1 kinase that is normally under the control of the calmodulin-regulated kinase.
Patel
R
R
Department of Physiology, University College London, United Kingdom.
Whitaker
M
M
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D007700:Kinetics; D008845:Microinjections; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D019319:Okadaic Acid; D009865:Oocytes / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D012617:Sea Urchins / Q000196:embryology; D015398:Signal Transduction
D004988:Ethers, Cyclic; D019319:Okadaic Acid; D004533:Egtazic Acid; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium