The adaptor molecule disabled-2 links the transforming growth factor β receptors to the Smad pathway

Barbara A. Hocevar, Abdelkrim Smine, Xiang Xi Xu, Philip H. Howe

Research output: Contribution to journalArticle

191 Scopus citations

Abstract

Using a genetic complementation approach we have identified disabled-2 (Dab2), a structural homolog of the Dabl 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.

Original languageEnglish (US)
Pages (from-to)2789-2801
Number of pages13
JournalEMBO Journal
Volume20
Issue number11
DOIs
StatePublished - Jun 1 2001

Keywords

  • Dab
  • Smad
  • Tgfβ

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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