The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect
Open accessAbstract
Pyruvate kinase M2 (PKM2) is upregulated in multiple cancer types and contributes to the Warburg effect by unclear mechanisms. Here we demonstrate that EGFR-activated ERK2 binds directly to PKM2 Ile 429/Leu 431 through the ERK2 docking groove and phosphorylates PKM2 at Ser 37, but does not phosphorylate PKM1. Phosphorylated PKM2 Ser 37 recruits PIN1 for cis–trans isomerization of PKM2, which promotes PKM2 binding to importin α5 and translocating to the nucleus. Nuclear PKM2 acts as a coactivator of β-catenin to induce c-Myc expression, resulting in the upregulation of GLUT1, LDHA and, in a positive feedback loop, PTB-dependent PKM2 expression. Replacement of wild-type PKM2 with a nuclear translocation-deficient mutant (S37A) blocks the EGFR-promoted Warburg effect and brain tumour development in mice. In addition, levels of PKM2 Ser 37 phosphorylation correlate with EGFR and ERK1/2 activity in human glioblastoma specimens. Our findings highlight the importance of nuclear functions of PKM2 in the Warburg effect and tumorigenesis.
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Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Self-citationRegulation of cancer cell metabolism
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Otto Warburg's contributions to current concepts of cancer metabolism
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The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
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Self-citationCancer cell metabolism: warburg and beyond
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PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis
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Palsson-McDermott, E. M., Curtis, A. M., Goel, G., Lauterbach, M. A. R., Sheedy, F. J., Gleeson, L. E., van den Bosch, M. W. M., Quinn, S. R., Domingo-Fernandez, R., Johnston, D. G. W., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.005 · Cited by 1,397
ERK signalling: A master regulator of cell behaviour, life and fate
Lavoie, H., Gagnon, J., & Therrien, M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0255-7 · Cited by 1,185
Fong, M. Y., Zhou, W., Liu, L., Alontaga, A. Y., Chandra, M., Ashby, J., Chow, A., O’Connor, S. T. F., Li, S., Chin, A. R., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3094 · Cited by 1,118
The Global Phosphorylation Landscape of SARS-CoV-2 Infection
Bouhaddou, M., Memon, D., Meyer, B., White, K. M., Rezelj, V. V., Correa Marrero, M., Polacco, B. J., Melnyk, J. E., Ulferts, S., Kaake, R. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.034 · Cited by 1,020
Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma
Feng, J., Li, J., Wu, L., Yu, Q., Ji, J., Wu, J., Dai, W., & Guo, C. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01629-4 · Cited by 699
Metadata
- Authors
- Yang, W., Zheng, Y., Xia, Y., Ji, H., Chen, X., Guo, F., Lyssiotis, C. A., Aldape, K., Cantley, L. C., & Lu, Z.
- Venue
- Nature Cell Biology
- Published
- 2012-11-25
- Volume
- 14
- Issue
- 12
- Pages
- 1295-1304
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1969836970
- Cited by
- 918
- References
- 7
- FWCI
- 12.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Yang, W., Zheng, Y., Xia, Y., Ji, H., Chen, X., Guo, F., Lyssiotis, C. A., Aldape, K., Cantley, L. C., & Lu, Z. (2012). ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nature Cell Biology. https://doi.org/10.1038/ncb2629
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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