p21-activated Kinase 2 (PAK2) Inhibits TGF-β Signaling in Madin-Darby Canine Kidney (MDCK) Epithelial Cells by Interfering with the Receptor-Smad Interaction *
Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 287, Issue: 17, Page: 13705-13712
2012
- 25Citations
- 22Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations25
- Citation Indexes25
- 25
- CrossRef18
- Captures22
- Readers22
- 22
Article Description
TGF-β (transforming growth factor β) plays a variety of cellular functions mainly through the Smad pathway. Phosphorylation of the carboxyl SXS motif in R-Smads (Smad2 and Smad3) by the type I receptor TβRI is a key step for their activation. It has been reported that the serine/threonine kinase PAK2 (p21-activated kinase 2) can mediate TGF-β signaling in mesenchymal cells. Here, we report that PAK2 restricts TGF-β-induced Smad2/3 activation and transcriptional responsiveness in MDCK epithelial cells. Mechanistically, PAK2 associates with Smad2 and Smad3 in a kinase activity-dependent manner and blocks their activation. PAK2 phosphorylates Smad2 at Ser-417, which is adjacent to the L3 loop that contributes to the TβRI-R-Smad association. Consistently, substitution of Ser-417 with glutamic acid attenuates the interaction of Smad2 with TβRI. Together, our results indicate that PAK2 negatively modulate TGF-β signaling by attenuating the receptor-Smad interaction and thus Smad activation.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0021925820529438; http://dx.doi.org/10.1074/jbc.m112.346221; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84859945472&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/22393057; http://www.jbc.org/lookup/doi/10.1074/jbc.M112.346221; https://syndication.highwire.org/content/doi/10.1074/jbc.M112.346221; https://linkinghub.elsevier.com/retrieve/pii/S0021925820529438; https://dx.doi.org/10.1074/jbc.m112.346221
American Society for Biochemistry & Molecular Biology (ASBMB)
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