Signaling crosstalk between TGFβ and Dishevelled/Par1b

Research output: Contribution to journalJournal articleResearchpeer-review

  • Anant Mamidi
  • M Inui
  • A Manfrin
  • S Soligo
  • E Enzo
  • M Aragona
  • M Cordenonsi
  • O Wessely
  • S Dupont
  • S Piccolo
Crosstalk of signaling pathways is critical during metazoan development and adult tissue homeostasis. Even though the transforming growth factor-beta (TGFβ) transduction cascade is rather simple, in vivo responsiveness to TGFβ ligands is tightly regulated at several steps. As such, TGFβ represents a paradigm for how the activity of one signaling system is modulated by others. Here, we report an unsuspected regulatory step involving Dishevelled (Dvl) and Par1b (also known as MARK2). Dvl and Par1b cooperate to enable TGFβ/bone morphogenetic protein (BMP) signaling in Xenopus mesoderm development and TGFβ responsiveness in mammalian cells. Mechanistically, the assembly of the Par1b/Dvl3/Smad4 complex is fostered by Wnt5a. The association of Smad4 to Dvl/Par1 prevents its inhibitory ubiquitination by ectodermin (also known as transcriptional intermediary factor 1 gamma or tripartite motif protein 33). We propose that this crosstalk is relevant to coordinate TGFβ responses with Wnt-noncanonical and polarity pathways.
Original languageEnglish
JournalCell Death and Differentiation
Volume19
Issue number10
Pages (from-to)1689-97
Number of pages9
ISSN1350-9047
DOIs
Publication statusPublished - Oct 2012
Externally publishedYes

    Research areas

  • Adaptor Proteins, Signal Transducing, Animals, Bone Morphogenetic Proteins, Cell Line, Embryo, Nonmammalian, HEK293 Cells, Humans, Phosphoproteins, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, RNA Interference, RNA, Small Interfering, Signal Transduction, Smad4 Protein, Transcription Factors, Transforming Growth Factor beta, Ubiquitination, Wnt Proteins, Xenopus

ID: 46502293