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TGF‐β receptor‐activated p38 MAP kinase mediates Smad‐independent TGF‐β responses
Author(s) -
Yu Li,
Hébert Mindy C.,
Zhang Ying E.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf366
Subject(s) - smad , tgf beta receptor 2 , biology , r smad , transforming growth factor beta , smad2 protein , microbiology and biotechnology , tgf beta signaling pathway , signal transduction , transforming growth factor, beta 3 , transforming growth factor , receptor , endoglin , cancer research , tgf alpha , growth factor , biochemistry , stem cell , cd34
Through the action of its membrane‐bound type I receptors, transforming growth factor‐β (TGF‐β) elicits a wide range of cellular responses that regulate cell proliferation, differentiation and apoptosis. Many of the signaling responses induced by TGF‐β are mediated by Smad proteins, but certain evidence has suggested that TGF‐β can also signal independently of Smads. We found in mouse mammary epithelial (NMuMG) cells, which respond to TGF‐β treatment in multiple ways, that TGF‐β‐induced activation of p38 MAP kinase is required for TGF‐β‐induced apoptosis, epithelial‐to‐mesenchymal transition (EMT), but not growth arrest. We further demonstrated that activation of p38 is independent of Smads using a mutant type I receptor, which is incapable of activating Smads but still retains the kinase activity. This mutant receptor is sufficient to activate p38 and cause NMuMG cells to undergo apoptosis. However, it is not sufficient to induce EMT. These results indicate that TGF‐β receptor signals through multiple intracellular pathways and provide first‐hand biochemical evidence for the existence of Smad‐independent TGF‐β receptor signaling.