The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
p38 mitogen-activated protein kinase is required for TGFβ-mediated fibroblastic transdifferentiation and cell migration
Abstract
Transforming growth factor β (TGFβ) contributes to tumor progression by inducing an epithelial to mesenchymal transdifferentiation(EMT) and cell migration. We found that TGFβ-induced EMT was blocked by inhibiting activation of p38 mitogen-activated protein kinase (MAPK) with H-7,a protein kinase C inhibitor, and with SB202190, a direct inhibitor of p38MAPK. Inhibition of the p38MAPK pathway affected TGFβ-mediated phosphorylation of ATF2, but did not inhibit phosphorylation of Smad2. SB202190 impaired TGFβ-mediated changes in cell shape and reorganization of the actin cytoskeleton. Forced expression of dominant-negative (DN) MAPK kinase 3 (MKK3) inhibited TGFβ-mediated activation of p38MAPK and EMT. Expression of DN-p38α impaired TGFβ-induced EMT. Inhibition of p38MAPK blocked TGFβ-induced migration of non-tumor and tumor mammary epithelial cells. TGFβ induced activation of the p38MAPK pathway within 15 minutes. Expression of TGFβ type II (TβRII) and type I(TβRI/Alk5) kinase-inactive receptors blocked EMT and activation of p38MAPK, whereas expression of constitutively active Alk5-T204D resulted in EMT and phosphorylation of MKK3/6 and p38MAPK. Finally, dominant-negative Rac1N17 blocked TGFβ-induced activation of the p38MAPK pathway and EMT,suggesting that Rac1 mediates activation of the p38MAPK pathway. These studies suggest that the p38MAPK pathway is required for TGFβ-mediated EMT and cell migration.
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Cites
Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response
Ashcroft, G. S., Yang, X., Glick, A. B., Weinstein, M., Letterio, J. J., Mizel, D. E., Anzano, M., Greenwell-Wild, T., Wahl, S. M., Deng, C., et al. (1999) · Nature Cell Biology · doi:10.1038/12971 · Cited by 911
Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta.
Postlethwaite, A. E., Keski-Oja, J., Moses, H. L., & Kang, A. H. (1987) · The Journal of experimental medicine · doi:10.1084/jem.165.1.251 · Cited by 777
Cui, W., Fowlis, D. J., Bryson, S., Duffie, E., Ireland, H., Balmain, A., & Akhurst, R. J. (1996) · Cell · doi:10.1016/s0092-8674(00)80127-0 · Cited by 628
Cited by
TGF-β: the master regulator of fibrosis
Meng, X.-M., Nikolic-Paterson, D. J., & Lan, H. Y. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.48 · Cited by 3,528
TGF-β-induced epithelial to mesenchymal transition
Xu, J., Lamouille, S., & Derynck, R. (2009) · Cell Research · doi:10.1038/cr.2009.5 · Cited by 2,804
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721
Tackling the cancer stem cells — what challenges do they pose?
Pattabiraman, D. R., & Weinberg, R. A. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4253 · Cited by 990
Regulation of the Polarity Protein Par6 by TGFß Receptors Controls Epithelial Cell Plasticity
Ozdamar, B., Bose, R., Barrios-Rodiles, M., Wang, H.-R., Zhang, Y., & Wrana, J. L. (2005) · Science · doi:10.1126/science.1105718 · Cited by 881
Metadata
- Authors
- Bakin, A. V., Rinehart, C., Tomlinson, A. K., & Arteaga, C. L.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2002-08-01
- Volume
- 115
- Issue
- 15
- Pages
- 3193-3206
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1930083400
- Cited by
- 431
- References
- 3
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bakin, A. V., Rinehart, C., Tomlinson, A. K., & Arteaga, C. L. (2002). p38 mitogen-activated protein kinase is required for TGFβ-mediated fibroblastic transdifferentiation and cell migration. Journal of Cell Science. https://doi.org/10.1242/jcs.115.15.3193
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