CoChat
Sign Up
Cited by 323Developmental Biology and Gene RegulationProtein Kinase Regulation and GTPase SignalingMelanoma and MAPK Pathways

Extracellular signal-regulated kinase 2 is necessary for mesoderm differentiation

Open access
Yao, Yao, Li, Wei, Wu, Junwei, Germann, Ursula A., Su, Michael S. S., Kuida, Keisuke, Boucher, Diane M.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2134254100PMC PMC240691
Open this paper in CoChat — free account

Abstract

The extracellular signal-regulated kinase (ERK) is a component of the mitogen-activated protein kinase cascade. Exon 2 of erk2 was deleted by homologous recombination and resulted in embryonic lethality at embryonic day 6.5. erk2 mutant embryos did not form mesoderm and showed increased apoptosis but comparable levels of BrdUrd incorporation, indicating a defect in differentiation. erk2 null embryonic stem (ES) cells exhibited reduced total ERK activity upon serum stimulation, augmented ERK1 phosphorylation, and decreased downstream p90Rsk phosphorylation and activity; yet ES cell proliferation was unaffected. Mutant ES cells were capable of forming mesoderm; however, treatment of mutant ES cells with the mitogen-activated protein kinase kinase inhibitor PD184352 decreased total ERK activity and expression of the mesodermal marker brachyury , suggesting that ERK1 can compensate for ERK2 in vitro . Normal embryos at embryonic day 6.5 expressed activated ERK1/2 in the extraembryonic ectoderm, whereas erk2 mutant embryos had no detectable activated ERK1/2 in this region, suggesting that activated ERK1 was not expressed, and therefore cannot compensate for loss of ERK2 in vivo . These data indicate that ERK2 plays an essential role in mesoderm differentiation during embryonic development.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.2134254100

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Embryonic lethality of ERK2 null mice appears to be strain-specific and/or related to the design of the knockout allele; some reported failed early mesodermal differentiation while others reported mis-regulation of placental development.

    “Embryonic lethality of the ERK2 null mice appears to be strain-specific and/or related to the design of the knockout allele; some having reported evidence of failed early mesodermal differentiation while others reporting mis-regulation of placental development10,11.”

    From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [10]

  • Loss of ERK2 in null animals causes catastrophic defects early in mouse development or at later developmental stages in the mouse placenta leading to early fetal death.

    “Other studies have shown that loss of ERK2 in null animals causes catastrophic defects early in mouse development10 or at later developmental stages in the mouse placenta leading to early fetal death8,11.”

    From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [10]

  • All of these studies point to the specific importance of ERK2 during development since ERK1 did not compensate for the loss of ERK2.

    “All of these studies point to the specific importance of ERK2 during development since in each experimental paradigm, ERK1 did not compensate for the loss of ERK2.”

    From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [10]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 27

  1. [1]Sugiura, N., Suga, T., Ozeki, Y., Mamiya, G. & Takishima, K. (1997) J. Biol. Chem. 272 21575–21581. [DOI] [PubMed] [Google Scholar]
  2. [2]Lewis, T. S., Shapiro, P. S. & Ahn, N. G. (1998) Adv. Cancer Res. 74 49–139. [DOI] [PubMed] [Google Scholar]
  3. [3]Lavoie, J. N., Rivard, N., L'Allemain, G. & Pouyssegur, J. (1996) Prog. Cell Cycle Res. 2, 49–58. [DOI] [PubMed] [Google Scholar]
  4. [4]Whitmarsh, A. J. & Davis, R. J. (2000) Nature 403 255–256. [DOI] [PubMed] [Google Scholar]
  5. [5]Traverse, S., Gomez, N., Paterson, H., Marshall, C. & Cohen, P. (1992) Biochem. J. 288 351–355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. [6]Kahan, C., Seuwen, K., Meloche, S. & Pouyssegur, J. (1992) J. Biol. Chem. 267 13369–13375. [PubMed] [Google Scholar]
  7. [7]Le Gall, M., Chambard, J. C., Breittmayer, J. P., Grall, D., Pouyssegur, J. & Van Obberghen-Schilling, E. (2000) Mol. Biol. Cell 11 1103–1112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. [8]Zugasti, O., Rul, W., Roux, P., Peyssonnaux, C., Eychene, A., Franke, T. F., Fort, P. & Hibner, U. (2001) Mol. Cell. Biol. 21 6706–6717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. [9]Schaeffer, H. J., Catling, A. D., Eblen, S. T., Collier, L. S., Krauss, A. & Weber, M. J. (1998) Science 281 1668–1671. [DOI] [PubMed] [Google Scholar]
  10. [10]Pages, G., Guerin, S., Grall, D., Bonino, F., Smith, A., Anjuere, F., Auberger, P. & Pouyssegur, J. (1999) Science 286 1374–1377. [DOI] [PubMed] [Google Scholar]
  11. [11]Mazzucchelli, C., Vantaggiato, C., Ciamei, A., Fasano, S., Pakhotin, P., Krezel, W., Welzl, H., Wolfer, D. P., Pages, G., Valverde, O., et. al. (2002) Neuron 34 807–820. [DOI] [PubMed] [Google Scholar]
  12. [12]Jirmanova, L., Afanassieff, M., Gobert-Gosse, S., Markossian, S. & Savatier, P. (2002) Oncogene 21 5515–5528. [DOI] [PubMed] [Google Scholar]
  13. [14]Wiles, M. V. & Johansson, B. M. (1999) Exp. Cell Res. 247 241–248. [DOI] [PubMed] [Google Scholar]
  14. [15]Proetzel, G. & Wiles, M. (2002) Methods Mol. Biol. 185 17–26. [DOI] [PubMed] [Google Scholar]
  15. [16]Brown, D., Wagner, D., Li, X., Richardson, J. A. & Olson, E. N. (1999) Development (Cambridge, U.K.) 126 4317–4329. [DOI] [PubMed] [Google Scholar]
  16. [17]Graves, L. M., Northrop, J. L., Potts, B. C., Krebs, E. G. & Kimelman, D. (1994) Proc. Natl. Acad. Sci. USA 91 1662–1666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. [18]Gotoh, Y., Masuyama, N., Suzuki, A., Ueno, N. & Nishida, E. (1995) EMBO J. 14 2491–2498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. [19]Umbhauer, M., Penzo-Mendez, A., Clavilier, L., Boucaut, J. & Riou, J. (2000) J. Cell Sci. 113 2865–2875. [DOI] [PubMed] [Google Scholar]
  19. [20]Amaya, E., Musci, T. J. & Kirschner, M. W. (1991) Cell 66 257–270. [DOI] [PubMed] [Google Scholar]
  20. [21]Amaya, E., Stein, P. A., Musci, T. J. & Kirschner, M. W. (1993) Development (Cambridge, U.K.) 118 477–487. [DOI] [PubMed] [Google Scholar]
  21. [22]Arsenian, S., Weinhold, B., Oelgeschlager, M., Ruther, U. & Nordheim, A. (1998) EMBO J. 17 6289–6299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. [23]Weinhold, B., Schratt, G., Arsenian, S., Berger, J., Kamino, K., Schwarz, H., Ruther, U. & Nordheim, A. (2000) EMBO J. 19 5835–5844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. [24]Fluck, M., Booth, F. W. & Waxham, M. N. (2000) Biochem. Biophys. Res. Commun. 270 488–494. [DOI] [PubMed] [Google Scholar]
  24. [25]Heidenreich, O., Neininger, A., Schratt, G., Zinck, R., Cahill, M. A., Engel, K., Kotlyarov, A., Kraft, R., Kostka, S., Gaestel, M. & Nordheim, A. (1999) J. Biol. Chem. 274 14434–14443. [DOI] [PubMed] [Google Scholar]
  25. [26]Rivera, V. M., Miranti, C. K., Misra, R. P., Ginty, D. D., Chen, R. H., Blenis, J. & Greenberg, M. E. (1993) Mol. Cell. Biol. 3 6260–6273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. [27]Savatier, P., Huang, S., Szekely, L., Wiman, K. G. & Samarut, J. (1994) Oncogene 9 809–818. [PubMed] [Google Scholar]
  27. [28]Ghosh, A. & Greenberg, M. E. (1995) Science 266 239–247. [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Related

Authors
Yao, Y., Li, W., Wu, J., Germann, U. A., Su, M. S. S., Kuida, K., & Boucher, D. M.
Affiliations
  • Vertex Pharmaceuticals (United States) (US)
  • Northwestern University (US)
Corresponding author
Kuida, Keisuke
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-10-17
Volume
100
Issue
22
Pages
12759-12764
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2134254100
PMC
PMC240691
OpenAlex
W2039397457
Cited by
323
References
29
Citations by year
2026: 8 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 11 · 2018: 11 · 2017: 11 · 2016: 13 · 2015: 22 · 2014: 11 · 2013: 18 · 2012: 31
FWCI
4.38
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
ERK2, extracellular signal-regulated kinase, mesoderm differentiation, mitogen-activated protein kinase cascade, embryonic lethality, apoptosis, embryonic stem cells, Brachyury, p90RSK, extraembryonic ectoderm, exon 2 deletion
MeSH terms
Animals, Benzamides, Cell Differentiation, Cell Division, Cell Line, Enzyme Inhibitors, Female, Heterozygote, Mesoderm, Mice, Inbred BALB C, Mice, Inbred C57BL, Stem Cells, Mice, Knockout, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review