SMURFs/NEDD4L ubiquitinate phosphorylated TGFBR1 and SMAD7

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
SMURF1 (Ebisawa et al. 2001), SMURF2 (Kavsak et al. 2000) or NEDD4L (Kuratomi et al. 2005) ubiquitin ligases, recruited to TGF-beta receptor complex through interaction with SMAD7, ubiquitinate both SMAD7 and/or TGF-beta receptor I (TGFBR1), targeting the complex for degradation. This was inferred from experiments using a recombinant mouse Smad7 with recombinant human ubiquitin ligases and TGF-beta receptors.
Literature References
PubMed ID Title Journal Year
11278251 Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation

Tanaka, K, Chiba, T, Miyazono, K, Murakami, G, Fukuchi, M, Ebisawa, T, Imamura, T

J Biol Chem 2001
15496141 NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor

Miyazono, K, Goto, K, Kuratomi, G, Shinozaki, M, Imamura, T, Komuro, A, Miyazawa, K

Biochem J 2005
11163210 Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation

Thomsen, GH, Wrana, JL, Bonni, S, Causing, CG, Rasmussen, RK, Zhu, H, Kavsak, P

Mol Cell 2000
Catalyst Activity

ubiquitin-protein transferase activity of TGFB1:TGFBR2:p-TGFBR1:SMAD7:SMURF/NEDD4L [plasma membrane]

Inferred From
Cite Us!