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PMID: 1323352 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Multiple roles for protein phosphatase 1 in regulating the Xenopus early embryonic cell cycle.

Molecular biology of the cell ·Vol. 3 ·No. 6 ·1992-06-00 ·Pages 687-98

Walker DH, DePaoli-Roach AA, Maller JL

Abstract

Using cytostatic factor metaphase II-arrested extracts as a model system, we show that protein phosphatase 1 is regulated during early embryonic cell cycles in Xenopus. Phosphatase 1 activity peaks during interphase and decreases shortly before the onset of mitosis. A second peak of activity appears in mitosis at about the same time that cdc2 becomes active. If extracts are inhibited in S-phase with aphidicolin, then phosphatase 1 activity remains high. The activity of phosphatase 1 appears to determine the timing of exit from S-phase and entry into M-phase; inhibition of phosphatase 1 by the specific inhibitor, inhibitor 2 (Inh-2), causes premature entry into mitosis, whereas exogenously added phosphatase 1 lengthens the interphase period. Analysis of DNA synthesis in extracts treated with Inh-2, but lacking the A- and B-type cyclins, shows that phosphatase 1 is also required for the process of DNA replication. These data indicate that phosphatase 1 is a component of the signaling pathway that ensures that M-phase is not initiated until DNA synthesis is complete.

MeSH Terms
Animals Aphidicolin/pharmacology DNA/biosynthesis,drug effects Ethers, Cyclic/pharmacology Mitosis/drug effects,physiology Okadaic Acid Phosphoprotein Phosphatases/antagonists & inhibitors,physiology Protein Phosphatase 1 Xenopus/embryology
Chemicals
Ethers, Cyclic Okadaic Acid Aphidicolin DNA Phosphoprotein Phosphatases Protein Phosphatase 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Walker D H
Howard Hughes Medical Institute, University of Colorado School of Medicine, Denver 80262.
DePaoli-Roach A A
Maller J L
References (65)
65 references, click to expand
  1. The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases.
    Cell. 1989 Jun 16;57(6):997-1007 PMID: 2544298
  2. Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog.
    Cell. 1987 May 22;49(4):559-67 PMID: 3032459
  3. The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
    Cell. 1988 Jul 29;54(3):423-31 PMID: 3293802
  4. The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation.
    Cell. 1986 Apr 25;45(2):261-8 PMID: 3516412
  5. Induction of nuclear envelope breakdown, chromosome condensation, and spindle formation in cell-free extracts.
    J Cell Biol. 1985 Aug;101(2):518-23 PMID: 3926780
  6. The protein phosphatases involved in cellular regulation. 2. Glycogen metabolism.
    Eur J Biochem. 1983 May 2;132(2):263-74 PMID: 6301825
  7. Cyclin synthesis drives the early embryonic cell cycle.
    Nature. 1989 May 25;339(6222):275-80 PMID: 2566917
  8. Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
    Mol Biol Cell. 1992 Jan;3(1):13-27 PMID: 1532335
  9. Constant expression and activity of protein phosphatase 2A in synchronized cells.
    Mol Cell Biol. 1991 Aug;11(8):4282-5 PMID: 1649390
  10. Molecular cloning and expression of the regulatory (RG1) subunit of the glycogen-associated protein phosphatase.
    J Biol Chem. 1991 Aug 25;266(24):15782-9 PMID: 1651919
  11. The cdc25 protein contains an intrinsic phosphatase activity.
    Cell. 1991 Oct 4;67(1):189-96 PMID: 1655274
  12. Involvement of protein phosphatases 1 and 2A in the control of M phase-promoting factor activity in starfish.
    J Cell Biol. 1989 Dec;109(6 Pt 2):3347-54 PMID: 2574724
  13. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
    Nature. 1989 Nov 2;342(6245):39-45 PMID: 2682257
  14. Dominoes and clocks: the union of two views of the cell cycle.
    Science. 1989 Nov 3;246(4930):614-21 PMID: 2683077
  15. The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.
    Cell. 1986 Dec 26;47(6):861-70 PMID: 2946420
  16. Cell cycle control genes in fission yeast and mammalian cells.
    Trends Genet. 1988 Oct;4(10):287-90 PMID: 3076289
  17. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement.
    Cell. 1988 Jul 1;54(1):17-26 PMID: 3289755
  18. Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+.
    Cell. 1988 Jul 29;54(3):433-9 PMID: 3293803
  19. Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs.
    Cell. 1986 Nov 21;47(4):577-87 PMID: 3779837
  20. cdc25+ functions as an inducer in the mitotic control of fission yeast.
    Cell. 1986 Apr 11;45(1):145-53 PMID: 3955656
  21. Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division.
    Cell. 1983 Jun;33(2):389-96 PMID: 6134587
  22. The catalytic subunits of protein phosphatase-1 and protein phosphatase 2A are distinct gene products.
    Eur J Biochem. 1984 Feb 1;138(3):635-41 PMID: 6319140
  23. Cyclin synthesis, modification and destruction during meiotic maturation of the starfish oocyte.
    Dev Biol. 1987 Nov;124(1):248-58 PMID: 15669148
  24. cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2.
    Mol Biol Cell. 1992 Jan;3(1):73-84 PMID: 1312880
  25. Purification and characterisation of the insulin-stimulated protein kinase from rabbit skeletal muscle; close similarity to S6 kinase II.
    Eur J Biochem. 1991 Aug 1;199(3):723-8 PMID: 1651243
  26. Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.
    EMBO J. 1991 Nov;10(11):3297-309 PMID: 1655416
  27. CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2A protein phosphatase.
    Mol Cell Biol. 1991 Nov;11(11):5767-80 PMID: 1656238
  28. Role for cyclin A in the dependence of mitosis on completion of DNA replication.
    Nature. 1991 Nov 28;354(6351):314-7 PMID: 1659666
  29. S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28.
    Nature. 1992 Jan 23;355(6358):365-8 PMID: 1731250
  30. The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
    Cell. 1991 Mar 8;64(5):903-14 PMID: 1825803
  31. Cyclin is degraded by the ubiquitin pathway.
    Nature. 1991 Jan 10;349(6305):132-8 PMID: 1846030
  32. An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs.
    Mol Cell Biol. 1991 Feb;11(2):1171-5 PMID: 1846666
  33. Cyclin promotes the tyrosine phosphorylation of p34cdc2 in a wee1+ dependent manner.
    EMBO J. 1991 May;10(5):1255-63 PMID: 1850698
  34. The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle.
    Nature. 1990 Nov 22;348(6299):302-8 PMID: 2123524
  35. Cyclin activation of p34cdc2.
    Cell. 1990 Nov 30;63(5):1013-24 PMID: 2147872
  36. One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis.
    Cell. 1990 Oct 5;63(1):33-46 PMID: 2170019
  37. Cell cycle oscillation of phosphatase inhibitor-2 in rat fibroblasts coincident with p34cdc2 restriction.
    Nature. 1990 Mar 1;344(6261):74-8 PMID: 2406614
  38. Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis.
    Cell. 1989 Jul 14;58(1):193-203 PMID: 2473839
  39. Okadaic acid, a specific protein phosphatase inhibitor, induces maturation and MPF formation in Xenopus laevis oocytes.
    FEBS Lett. 1989 Mar 13;245(1-2):91-4 PMID: 2538367
  40. Involvement of a type 1 protein phosphatase encoded by bws1+ in fission yeast mitotic control.
    Cell. 1989 Jun 16;57(6):1009-16 PMID: 2544292
  41. The structure and regulation of protein phosphatases.
    Annu Rev Biochem. 1989;58:453-508 PMID: 2549856
  42. The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization.
    Cell. 1989 Aug 11;58(3):485-97 PMID: 2569363
  43. Regulation of p34cdc2 protein kinase during mitosis.
    Cell. 1989 Jul 28;58(2):361-72 PMID: 2665944
  44. Regulation of MPF activity in vitro.
    Cell. 1988 Apr 22;53(2):185-95 PMID: 2834064
  45. In vivo actions of protein phosphatase inhibitor-2 in Xenopus oocytes.
    FEBS Lett. 1982 Dec 13;150(1):155-60 PMID: 7160468
  46. Okadaic acid mimics a nuclear component required for cyclin B-cdc2 kinase microinjection to drive starfish oocytes into M phase.
    J Cell Biol. 1991 Oct;115(2):337-44 PMID: 1655804
  47. Fluorescence studies on the interaction of inhibitor 2 and okadaic acid with the catalytic subunit of type 1 phosphoprotein phosphatases.
    Biochemistry. 1991 Oct 22;30(42):10280-7 PMID: 1657143
  48. mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2.
    Cell. 1991 Mar 22;64(6):1111-22 PMID: 1706223
  49. Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport.
    J Cell Biol. 1991 Oct;115(1):1-17 PMID: 1717476
  50. Regulation of p34CDC28 tyrosine phosphorylation is not required for entry into mitosis in S. cerevisiae.
    Nature. 1992 Jan 23;355(6358):368-71 PMID: 1731251
  51. Cyclin A and the retinoblastoma gene product complex with a common transcription factor.
    Nature. 1991 Jul 18;352(6332):249-51 PMID: 1830372
  52. cdc2 phosphorylation is required for its interaction with cyclin.
    EMBO J. 1991 Nov;10(11):3311-9 PMID: 1833185
  53. INH, a negative regulator of MPF, is a form of protein phosphatase 2A.
    Cell. 1991 Jan 25;64(2):415-23 PMID: 1846321
  54. Protein phosphatases: recent progress.
    Adv Second Messenger Phosphoprotein Res. 1991;23:1-121 PMID: 1847640
  55. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
    Cell. 1991 Oct 4;67(1):197-211 PMID: 1913817
  56. Cyclin is a component of maturation-promoting factor from Xenopus.
    Cell. 1990 Feb 9;60(3):487-94 PMID: 1967981
  57. The A- and B-type cyclin associated cdc2 kinases in Xenopus turn on and off at different times in the cell cycle.
    EMBO J. 1990 Sep;9(9):2865-75 PMID: 2143983
  58. Cdc2 H1 kinase is negatively regulated by a type 2A phosphatase in the Xenopus early embryonic cell cycle: evidence from the effects of okadaic acid.
    EMBO J. 1990 Mar;9(3):675-83 PMID: 2155777
  59. Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus.
    Cell. 1990 Jun 1;61(5):811-23 PMID: 2160859
  60. Distinct, essential roles of type 1 and 2A protein phosphatases in the control of the fission yeast cell division cycle.
    Cell. 1990 Oct 19;63(2):405-15 PMID: 2170029
  61. Fission yeast p13 blocks mitotic activation and tyrosine dephosphorylation of the Xenopus cdc2 protein kinase.
    Cell. 1989 Jul 14;58(1):181-91 PMID: 2473838
  62. Purification and characterization of a novel protein phosphatase highly specific for ribosomal protein S6.
    J Biol Chem. 1989 Jan 5;264(1):151-6 PMID: 2535837
  63. Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF.
    Cell. 1989 Mar 10;56(5):829-38 PMID: 2538242
  64. Dephosphorylation and activation of Xenopus p34cdc2 protein kinase during the cell cycle.
    Nature. 1989 Jun 22;339(6226):626-9 PMID: 2543932
  65. The bimG gene of Aspergillus nidulans, required for completion of anaphase, encodes a homolog of mammalian phosphoprotein phosphatase 1.
    Cell. 1989 Jun 16;57(6):987-96 PMID: 2544297
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.3.6.687
Published
1992-06-00
Pages
687-98
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC275623
Subset
IM
Grants
NIDDK NIH HHS · DK-36569 · United States
NIDDK NIH HHS · DK01690 · United States
NIGMS NIH HHS · GM-26743 · United States
External Links
PubMed source DOI: 10.1091/mbc.3.6.687 PMC Full Text View journal details
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