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A single missense mutant of Smad3 inhibits activation of both Smad2 and Smad3, and has a dominant negative effect on TGF‐β signals
Author(s) -
Goto Daisuke,
Yagi Ken,
Inoue Hirofumi,
Iwamoto Itsuo,
Kawabata Masahiro,
Miyazono Kohei,
Kato Mitsuyasu
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00658-9
Subject(s) - missense mutation , mutant , phosphorylation , hacat , transforming growth factor , wild type , chemistry , microbiology and biotechnology , bone morphogenetic protein , mutation , biology , cancer research , gene , genetics , biochemistry , cell culture
A missense mutation of Smad2 identified in cancer cells was reconstructed on the corresponding residue of Smad3. This mutant, Smad3D407E, was not phosphorylated by the constitutively active form of type I receptor for transforming growth factor‐β (TGF‐β), and inhibited the phosphorylation of co‐expressed wild‐type Smad2 and Smad3. This mutant also had a dominant negative effect on the growth inhibition of HaCaT cells and on the expression of p3TP‐lux reporter gene induced by TGF‐β. However, it did not alter the phosphorylation of Smad1 induced by the constitutively active form of the bone morphogenetic protein type IA receptor. These findings showed that a single missense mutation in Smad3 could specifically block TGF‐β signals by preventing activation of both Smad2 and Smad3.