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The adaptor molecule Disabled‐2 links the transforming growth factor β receptors to the Smad pathway
Author(s) -
Hocevar Barbara A.,
Smine Abdelkrim,
Xu XiangXi,
Howe Philip H.
Publication year - 2001
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/20.11.2789
Subject(s) - smad , biology , signal transducing adaptor protein , smad2 protein , microbiology and biotechnology , signal transduction , phosphorylation , tgf beta receptor 2 , r smad , transforming growth factor beta , receptor , tgf alpha , genetics , epidermal growth factor
Using a genetic complementation approach we have identified disabled‐2 (Dab2), a structural homolog of the Dab1 adaptor molecule, as a critical link between the transforming growth factor β (TGFβ) receptors and the Smad family of proteins. Expression of wild‐type Dab2 in a TGFβ‐signaling mutant restores TGFβ‐mediated Smad2 phosphorylation, Smad translocation to the nucleus and Smad‐dependent transcriptional responses. TGFβ stimulation triggers a transient increase in association of Dab2 with Smad2 and Smad3, which is mediated by a direct interaction between the N‐terminal phosphotyrosine binding domain of Dab2 and the MH2 domain of Smad2. Dab2 associates with both the type I and type II TGFβ receptors in vivo , suggesting that Dab2 is part of a multiprotein signaling complex. Together, these data indicate that Dab2 is an essential component of the TGFβ signaling pathway, aiding in transmission of TGFβ signaling from the TGFβ receptors to the Smad family of transcriptional activators.