Open Close
Reference
Citation
Haerry, T.E. (2010). The interaction between two TGF-beta type I receptors plays important roles in ligand binding, SMAD activation, and gradient formation.  Mech. Dev. 127(7-8): 358--370.
FlyBase ID
FBrf0211154
Publication Type
Research paper
Abstract

The goal of this report is to elucidate the contributions of the Drosophila TGF-beta type I receptors TKV and SAX to the activity gradient formed by the two BMP family members DPP and GBB that play important roles in growth and patterning of imaginal discs. Binding studies display preferential interactions of DPP and GBB with homodimers of TKV or SAX, respectively, but also low affinities of both ligands to heterodimers. Inside the cell, constitutively activated forms of both TKV and SAX can ectopically phosphorylate the SMAD transcription factor MAD. However, MAD phosphorylated by homodimers of activated SAX or certain mutant forms of TKV localizes to the nucleus without changing the expression of downstream genes. Differences in signaling between SAX and TKV can be localized to amino acid residues within an area that has been shown to influence complexes formation between type I and type II receptors. The finding that the type II receptor PUT but not activated forms of SAX can enhance signaling of a pseudo-activated MAD-SDVD, which cannot be phosphorylated at the C-terminus, suggests a model, where activation of SMADs requires the presence of type II receptors and a second activation step in addition to C-terminal phosphorylation. Complete activation of MAD can only occur in tetrameric complexes of type II receptors in combination with SAX-TKV heterodimers or TKV homodimers but not SAX homodimers. Since TKV is not distributed equally in wing discs, heterodimers of SAX and TKV play an important role in extending the BMP activity gradient by facilitating DPP diffusion and assisting GBB signaling through functional complexes with type II receptors.

PubMed ID
PubMed Central ID
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mech. Dev.
    Title
    Mechanisms of Development
    Publication Year
    1990-
    ISBN/ISSN
    0925-4773
    Data From Reference