Home LiteratureArticle Details
PMID: 1384061 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Oncogenic ras triggers the activation of 42-kDa mitogen-activated protein kinase in extracts of quiescent Xenopus oocytes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 20 ·1992-10-15 ·Pages 9831-5

Shibuya EK, Polverino AJ, Chang E, Wigler M, Ruderman JV

Abstract

Quiescent, full-grown Xenopus oocytes, which are arrested at the G2/M border of meiosis, contain an inactive 42-kDa mitogen-activated protein kinase (p42MAPK) that is activated when oocytes are stimulated to resume the meiotic cell cycle. We have made extracts from these oocytes that respond to four cell cycle activators: oncogenic [Val12]Ras protein, clam cyclins A delta 60 and B delta 97, and the phosphatase inhibitor okadaic acid. All four induce the tyrosine phosphorylation and activation of p42MAPK. Both cyclins and okadaic acid, but not [Val12]Ras, also lead to activation of the endogenous cyclin B/cdc2 kinase complexes in extracts of quiescent oocytes. Using extracts prepared from cycloheximide-arrested interphase cells, we show that although p42MAPK activation can occur in response to cyclin-activated cdc2, the Ras-induced activation of p42MAPK occurs without intervening cdc2 activation. Neither the nononcogenic [Gly12]Ras nor [Val12,Arg186]Ras, a mutant that lacks the C-terminal consensus sequence directing prenylation and subsequent membrane association, is an effective activator of p42MAPK in vitro.

Related Genes
Ras
MeSH Terms
Animals Base Sequence Cyclins/pharmacology Cycloheximide/pharmacology Enzyme Activation Meiosis/drug effects Microinjections Mitogen-Activated Protein Kinase 1 Molecular Sequence Data Oligodeoxyribonucleotides/chemistry Oocytes/enzymology Phosphotyrosine Protein Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins p21(ras)/genetics,pharmacology Recombinant Fusion Proteins/pharmacology Tyrosine/analogs & derivatives,metabolism Xenopus laevis/embryology
Chemicals
Cyclins Oligodeoxyribonucleotides Recombinant Fusion Proteins Phosphotyrosine Tyrosine Cycloheximide Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Mitogen-Activated Protein Kinase 1 Proto-Oncogene Proteins p21(ras)
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shibuya E K
Department of Anatomy and Cell Biology, Harvard Medical School, Boston, MA 02115.
Polverino A J
Chang E
Wigler M
Ruderman J V
References (65)
65 references, click to expand
  1. SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits.
    Genes Dev. 1988 May;2(5):517-27 PMID: 3290050
  2. ras genes.
    Annu Rev Biochem. 1987;56:779-827 PMID: 3304147
  3. A sensitive method for detection of calmodulin-dependent protein kinase II activity in sodium dodecyl sulfate-polyacrylamide gel.
    Anal Biochem. 1989 Nov 15;183(1):139-43 PMID: 2559625
  4. Oncogenes, growth factors, and signal transduction.
    N Engl J Med. 1989 Nov 16;321(20):1383-91 PMID: 2682241
  5. Mutants of H-ras that interfere with RAS effector function in Saccharomyces cerevisiae.
    EMBO J. 1989 Oct;8(10):3039-44 PMID: 2684634
  6. Molecular cloning and characterization of the mRNA for cyclin from sea urchin eggs.
    EMBO J. 1987 Oct;6(10):2987-95 PMID: 2826125
  7. Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells.
    Nature. 1985 Jan 17-23;313(5999):241-3 PMID: 3918269
  8. Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
    J Morphol. 1972 Feb;136(2):153-79 PMID: 4109871
  9. Relative roles of the pituitary, follicle cells, and progesterone in the induction of oocyte maturation in Rana pipiens.
    J Exp Zool. 1967 Dec;166(3):365-75 PMID: 5583339
  10. The p21 ras C-terminus is required for transformation and membrane association.
    Nature. 1984 Aug 16-22;310(5978):583-6 PMID: 6087162
  11. Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells.
    J Mol Appl Genet. 1983;2(2):173-80 PMID: 6308118
  12. Functional homology of mammalian and yeast RAS genes.
    Cell. 1985 Jan;40(1):19-26 PMID: 2981628
  13. Regulated expression and phosphorylation of a possible mammalian cell-cycle control protein.
    Nature. 1988 Jun 16;333(6174):676-9 PMID: 3287181
  14. Oncogenic ras protein induces meiotic maturation of amphibian oocytes in the presence of protein synthesis inhibitors.
    FEBS Lett. 1988 Jul 18;234(2):426-30 PMID: 3292293
  15. 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
  16. Purification and characterization of human H-ras proteins expressed in Escherichia coli.
    Mol Cell Biol. 1985 May;5(5):1015-24 PMID: 3923330
  17. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  18. The use of Xenopus oocytes for the expression of cloned genes.
    Methods Enzymol. 1983;101:370-86 PMID: 6193395
  19. Proteins of pore complex--lamina structures from nuclei and nuclear membranes.
    Methods Enzymol. 1983;96:597-608 PMID: 6318023
  20. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP.
    Mol Cell Biol. 1988 Aug;8(8):3235-43 PMID: 3145408
  21. Metal chelate affinity chromatography, a new approach to protein fractionation.
    Nature. 1975 Dec 18;258(5536):598-9 PMID: 1678
  22. Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases.
    Cell. 1992 Mar 20;68(6):1031-40 PMID: 1312392
  23. ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK.
    Cell. 1992 Mar 20;68(6):1041-50 PMID: 1312393
  24. Xenopus MAP kinase activator: identification and function as a key intermediate in the phosphorylation cascade.
    EMBO J. 1992 Mar;11(3):973-82 PMID: 1312468
  25. Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes.
    Science. 1992 Jan 10;255(5041):212-5 PMID: 1313186
  26. Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein.
    EMBO J. 1992 Feb;11(2):569-74 PMID: 1371463
  27. Evidence for a Ras-dependent extracellular signal-regulated protein kinase (ERK) cascade.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6924-8 PMID: 1495981
  28. Growth factor signaling: where is the specificity?
    Cell. 1992 Mar 20;68(6):995-7 PMID: 1547509
  29. Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies.
    Cell Regul. 1991 May;2(5):357-71 PMID: 1654126
  30. The cdc25 protein contains an intrinsic phosphatase activity.
    Cell. 1991 Oct 4;67(1):189-96 PMID: 1655274
  31. Control of the cell cycle in early embryos.
    Cold Spring Harb Symp Quant Biol. 1991;56:495-502 PMID: 1668087
  32. In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase.
    Nature. 1991 Jan 17;349(6306):251-4 PMID: 1702878
  33. Tyrosine phosphorylation and activation of homologous protein kinases during oocyte maturation and mitogenic activation of fibroblasts.
    Mol Cell Biol. 1991 May;11(5):2517-28 PMID: 1708093
  34. Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.
    Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142-6 PMID: 1712480
  35. Xenopus M phase MAP kinase: isolation of its cDNA and activation by MPF.
    EMBO J. 1991 Sep;10(9):2661-8 PMID: 1714387
  36. Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of src and ras actions.
    J Cell Biol. 1991 Nov;115(3):809-19 PMID: 1717492
  37. Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine.
    Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8845-9 PMID: 1717989
  38. Isoprenoid modification and plasma membrane association: critical factors for ras oncogenicity.
    Cancer Cells. 1991 Sep;3(9):331-40 PMID: 1751286
  39. Activation of p34cdc2 kinase by cyclin A.
    J Cell Biol. 1991 May;113(3):507-14 PMID: 1826688
  40. The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
    Cell. 1988 Jul 29;54(3):423-31 PMID: 3293802
  41. Autophosphorylation in vitro of recombinant 42-kilodalton mitogen-activated protein kinase on tyrosine.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9508-12 PMID: 1835084
  42. Both cyclin A delta 60 and B delta 97 are stable and arrest cells in M-phase, but only cyclin B delta 97 turns on cyclin destruction.
    EMBO J. 1991 Dec;10(13):4311-20 PMID: 1836759
  43. Cyclins and their partners during Xenopus oocyte maturation.
    Cold Spring Harb Symp Quant Biol. 1991;56:437-47 PMID: 1840257
  44. Tyrosine phosphorylation of p34cdc2 and p42 during meiotic maturation of Xenopus oocyte. Antagonistic action of okadaic acid and 6-DMAP.
    Development. 1991 Mar;111(3):813-20 PMID: 1879344
  45. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
    Cell. 1991 Oct 4;67(1):197-211 PMID: 1913817
  46. Rapid and efficient purification of native histidine-tagged protein expressed by recombinant vaccinia virus.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8972-6 PMID: 1924358
  47. Cell cycle tyrosine phosphorylation of p34cdc2 and a microtubule-associated protein kinase homolog in Xenopus oocytes and eggs.
    Mol Cell Biol. 1991 Apr;11(4):1965-71 PMID: 2005892
  48. Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells.
    Mol Cell Biol. 1990 Oct;10(10):5314-23 PMID: 2118993
  49. Cyclin activation of p34cdc2.
    Cell. 1990 Nov 30;63(5):1013-24 PMID: 2147872
  50. Activation of M-phase-specific histone H1 kinase by modification of the phosphorylation of its p34cdc2 and cyclin components.
    Genes Dev. 1990 Jan;4(1):9-17 PMID: 2155162
  51. ras proteins can induce meiosis in Xenopus oocytes.
    Cell. 1985 Dec;43(3 Pt 2):615-21 PMID: 2416466
  52. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
    Science. 1988 Jan 29;239(4839):487-91 PMID: 2448875
  53. Human cdc2 protein kinase is a major cell-cycle regulated tyrosine kinase substrate.
    Nature. 1988 Dec 22-29;336(6201):738-44 PMID: 2462672
  54. 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
  55. The role of cyclin B in meiosis I.
    J Cell Biol. 1989 Apr;108(4):1431-44 PMID: 2522454
  56. Dephosphorylation and activation of Xenopus p34cdc2 protein kinase during the cell cycle.
    Nature. 1989 Jun 22;339(6226):626-9 PMID: 2543932
  57. Cyclin synthesis drives the early embryonic cell cycle.
    Nature. 1989 May 25;339(6222):275-80 PMID: 2566917
  58. Mitotic control by metaphase-promoting factor and cdc proteins.
    J Cell Sci. 1989 Feb;92 ( Pt 2):131-5 PMID: 2674165
  59. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis.
    Nature. 1989 Nov 2;342(6245):39-45 PMID: 2682257
  60. Related proteins are phosphorylated at tyrosine in response to mitogenic stimuli and at meiosis.
    Mol Cell Biol. 1989 Jul;9(7):3143-7 PMID: 2779558
  61. Requirement for c-ras proteins during viral oncogene transformation.
    Nature. 1986 Apr 10-16;320(6062):540-3 PMID: 2938016
  62. 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
  63. Inhibition of growth factor-induced differentiation of PC12 cells by microinjection of antibody to ras p21.
    Nature. 1986 Feb 20-26;319(6055):680-2 PMID: 3005866
  64. Stabilization and enhancement of primary cytostatic factor (CSF) by ATP and NaF in amphibian egg cytosols.
    Dev Biol. 1988 Sep;129(1):253-64 PMID: 3261698
  65. Purification of maturation-promoting factor, an intracellular regulator of early mitotic events.
    Proc Natl Acad Sci U S A. 1988 May;85(9):3009-13 PMID: 3283736
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.20.9831
Published
1992-10-15
Pages
9831-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50227
Subset
IM
Grants
NICHD NIH HHS · HD23696 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.20.9831 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2