Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in <i>Xenopus laevis</i> oocytes

Goris, Jozef; Hermann, Jacques; Hendrix, Peter; Ozon, René; Merlevede, Wilfried

doi:10.1016/0014-5793(89)80198-x

Cited by 178 publications

(120 citation statements)

References 28 publications

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“…Because PP1s are highly conserved among different species, we decided to determine whether the inhibitory role of PfLRR1 on PP1 could be operative in cells. To address this point, we used Xenopus oocytes that are physiologi-cally arrested in G2/M prophase I and in which OA, a specific protein phosphatase inhibitor, induces GVBD (Goris et al, 1989). We observed that the microinjection of PfLRR1 to oocytes, similar to anti-PP1 antibodies and OA, promoted the progression of oocytes to M phase, inducing GVBD.…”

Section: Discussionmentioning

confidence: 99%

Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

Daher

Browaeys

Pierrot

et al. 2006

Molecular Microbiology

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SummaryThe protein called 'suppressor of the dis2 mutant ( sds22 + )' is an essential regulator of cell division in fission and budding yeasts, where its deletion causes mitotic arrest. Its role in cell cycle control appears to be mediated through the activation of protein phosphatase type 1 (PP1) in Schizosaccharomyces pombe . We have identified the Plasmodium falciparum Sds22 orthologue, which we designated PfLRR1 as it belongs to the leucine-rich repeat protein family. We showed by glutathione-S-transferase pull-down assay that the PfLRR1 gene product interacts with PfPP1, that the PfLRR1-PfPP1 complex is present in parasite extracts and that PfLRR1 inhibits PfPP1 activity. Functional studies in Xenopus oocytes revealed that PfLRR1 interacted with endogenous PP1 and overcame the G2/M cell cycle checkpoint by promoting progression to germinal vesicle breakdown (GVBD). Confirmatory results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies or okadaic acid. Taken together, these observations suggest that PfLRR1 can regulate the cell cycle by binding to PP1 and regulating its activity.

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Section: Discussionmentioning

confidence: 99%

Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

Daher

Browaeys

Pierrot

et al. 2006

Molecular Microbiology

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“…OA has been shown to activate latent cdc2 kinase in oocytes and early embryos (7,13,22). Since OA increased cdc2 kinase to some extent in metaphase extracts before cyclin protease was activated (Fig.…”

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confidence: 88%

“…In G2-arrested oocytes, cdc2 kinase is maintained in an inactive form due to phosphorylation of its catalytic subunit (6,11,14,18,20). OA has been shown to induce both dephosphorylation and activation of cdc2 kinase in starfish oocytes (22), and both events probably also occur in amphibians (7,13). The cdc2 phosphatase is not known, but it shares many features in common with phosphatase X: it is not sensitive to OA, does not require Ca2+, and is activated either by blocking type 2A phosphatase or by microinjecting the pure cdc2 kinase (5) (the so-called MPF amplification process).…”

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confidence: 99%

An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs.

et al. 1991

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Inhibition of okadaic acid-sensitive phosphatases released the cyclin degradation pathway from its inhibited state in extracts prepared from unfertilized Xenopus eggs arrested at the second meiotic metaphase. It also switched on cyclin protease activity in a permanent fashion in interphase extracts prepared from activated eggs. Even after cdc2 kinase inactivation, microinjection of okadaic acid-treated interphase extracts pushed G2-arrested recipient oocytes into the M phase, suggesting that the phosphatase inhibitor stabilizes the activity of an unidentified factor which shares in common with cdc2 kinase the maturation-promoting factor activity.Exit from the M phase of the cell cycle requires inactivation of maturation-promoting factor (MPF), a universal inducer of mitosis recently identified as a stoichiometric complex between a cdc2+-encoded protein kinase and cyclin B, a protein whose concentration oscillates during the cell cycle (12, 16). MPF inactivation requires cyclin proteolysis (21), which begins at the end of metaphase and is completed within a very short window of the cell cycle (25, 28). At least two protein kinases have been shown to be involved in the control of cyclin degradation. One is cdc2 kinase itself, which promotes the abrupt degradation of cyclin about 15 min after its addition to interphase extracts made from fertilized or activated Xenopus eggs (8). At the end of the M phase, after cyclin has been destroyed, cdc2 kinase is inactivated and so is the proteolysis machinery. The second one is c-mos protein kinase, a proto-oncogene-encoded protein kinase. In vertebrates, c-mos protein kinase acts as a cytostatic factor which prevents proteolytic degradation of cyclin and arrests unfertilized eggs at the second meiotic metaphase (24). On fertilization or parthenogenetic activation, a calcium-dependent process inactivates c-mos kinase, resulting in cyclin degradation (27). The dramatic effects of inactivation of either the cdc2 or c-mos protein kinase on cyclin degradation suggest the involvement of unidentified protein phosphatases in the control of cyclin proteolysis.Therefore, the cyclin degradation pathway may be viewed as a complex network of protein kinases and protein phosphatases controlling ultimately the activity of a cyclin protease. Here we show that okadaic acid (OA), a potent inhibitor of type 1 and type 2A phosphatases (1, 3), overcomes a c-mos kinase inhibition of the cyclin degradation pathway in calcium-free extracts prepared from metaphasearrested eggs, while it deregulates and switches on cyclin protease activity in a permanent fashion in interphase extracts prepared from activated eggs. This leads us to propose that an OA-inhibited phosphatase, most likely type 2A phosphatase, exerts a negative control on the cyclin degradation pathway. Moreover, microinjection of OA-treated extracts pushes G2-arrested recipient oocytes into the M * Corresponding author.phase, even after cdc2 kinase inactivation. This suggests that the phosphatase inhibitor stabilizes the activity of an u...

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“…2), compounds known to be inhibitors of PP2A [35-381. All the PTPases tested so far were insensitive towards okadaic acid [35,441, with the exception of the PTPase activity of PP2A, which was shown to be as sensitive towards okadaic acid as its Ser/Thr phosphatase activity [15, 36,451. Based on these findings, it is highly probable that the phosphatase has dual specificity.…”

Section: T-antigen-associated Pp2a Shows Okadaic Acid-sensitive Tyrosmentioning

confidence: 99%

Phosphatase 2A associated with polyomavirus small‐T or middle‐T antigen is an okadaic acid‐sensitive tyrosyl phosphatase

Cayla

Ballmer-Hofer

Merlevede

et al. 1993

European Journal of Biochemistry

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Papovavirus tumor antigens have been shown to associate with the cellular phosphoserinehreonine-specific protein phosphatase 2A (PP2A). We were interested in the consequences that Tantigen association might have on PP2A activity and so studies of the phosphatase activity in immunoprecipitates, prepared from polyoma virus-transformed or polyoma virus-infected mouse 3T3 fibroblasts, were performed. The phosphoserine/threonine phosphatase activity, measured with phosphorylase a as the substrate, showed all the characteristics of PP2A. It was stimulated by polycations, inhibited by fluoride or p-nitrophenyl phosphate, sensitive to okadaic acid and microcystin and insensitive to inhibitor-1 and inhibitor-2. Phosphotyrosyl phosphatase (PTPase) activity was associated with the middle-T/small-T-associated complex when reduced, carboxamidomethylated and maleylated lysozyme, phosphorylated exclusively on tyrosyl residues, was used as the substrate. This PTPase activity was as sensitive to okadaic acid as was the phosphorylase phosphatase activity ; it could be inhibited by phosphorylase a and did not dephosphorylate poly(G1u8nTyr2n). The level of middle-T/small-T-associated PTPase activity relative to the phosphorylase phosphatase activity was tenfold higher than that of the purified dimeric PP2A. A similar activity ratio was observed with the purified phosphatase after stimulation with a cellular protein, designated phosphotyrosyl phosphatase activator. These results suggest that the same enzyme may possess dual specificity. In contrast to the cellular trimeric PP2A, containing the 55-kDa putative regulatory subunit, the middle-Thmall-T-associated enzyme had low activity towards a retinoblastoma peptide phosphorylated by p3Pdc2. These results indicate how middle-Thmall-T might effect the activity of PP2A in polyoma virus-transformed cells.

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Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes

Cited by 178 publications

References 28 publications

Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs.

Phosphatase 2A associated with polyomavirus small‐T or middle‐T antigen is an okadaic acid‐sensitive tyrosyl phosphatase

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