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MAPKK-Independent Activation of p38α Mediated by TAB1-Dependent Autophosphorylation of p38α
Abstract
Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38α MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38α with TAB1 [transforming growth factor-β–activated protein kinase 1 (TAK1)–binding protein 1] leading to autophosphorylation and activation of p38α. We detected formation of a TRAF6-TAB1-p38α complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38α activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38α to various stimuli.
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Citations
Cites
Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms
Dérijard, B., Raingeaud, J., Barrett, T., Wu, I.-H., Han, J., Ulevitch, R. J., & Davis, R. J. (1995) · Science · doi:10.1126/science.7839144 · Cited by 1,555
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Cited by
Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases
Johnson, G. L., & Lapadat, R. (2002) · Science · doi:10.1126/science.1072682 · Cited by 4,295
Mitogen-activated protein kinases in apoptosis regulation
Wada, T., & Penninger, J. M. (2004) · Oncogene · doi:10.1038/sj.onc.1207556 · Cited by 1,432
Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1
Koh, A., Molinaro, A., Ståhlman, M., Khan, M. T., Schmidt, C., Mannerås-Holm, L., Wu, H., Carreras, A., Jeong, H., Olofsson, L. E., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.055 · Cited by 824
Diversity and versatility of p38 kinase signalling in health and disease
Canovas, B., & Nebreda, A. R. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00322-w · Cited by 657
Tau protein kinases: Involvement in Alzheimer's disease
Martin, L., Latypova, X., Wilson, C. M., Magnaudeix, A., Perrin, M.-L., Yardin, C., & Terro, F. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2012.06.003 · Cited by 631
Metadata
- Authors
- Ge, B., Gram, H., Di Padova, F., Huang, B., New, L., Ulevitch, R. J., Luo, Y., & Han, J.
- Venue
- Science
- Published
- 2002-02-15
- Volume
- 295
- Issue
- 5558
- Pages
- 1291-1294
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1751748906
- Cited by
- 534
- References
- 1
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
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- Ge, B., Gram, H., Di Padova, F., Huang, B., New, L., Ulevitch, R. J., Luo, Y., & Han, J. (2002). MAPKK-Independent Activation of p38α Mediated by TAB1-Dependent Autophosphorylation of p38α. Science. https://doi.org/10.1126/science.1067289
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