Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor.
Inactivation of bone morphogenetic protein signaling via mutation of the BMPR-IA TGF-beta superfamily type I receptor causes familial juvenile polyposis, an inherited gastrointestinal cancer predisposition syndrome. In an effort to provide new insight into the mechanism(s) of BMP-mediated tumor suppression, we employed a yeast two-hybrid screen to identify novel proteins ... that interact with the intracellular domain of BMPR-IA. 30/31 interacting clones encoded SAP49, a splicing factor that has been shown to be required for normal development in Caenorhabditis elegans. The remaining interacting clone was FKBP12.6, a known TGF-beta type I receptor interactor. The interaction between BMPR-IA and SAP49 was confirmed via coimmunoprecipitation in human cells. Mutational analysis demonstrated that the GS domain of the receptor and the conserved proline-rich domain of SAP49 were required for the interaction. Co-localization studies suggested that the interaction may occur at the inner leaflet of the nuclear membrane. These data suggest that BMPR-IA may interact with and modulate the activity of a developmentally relevant splicing factor.
Mesh Terms:
Blotting, Northern, Blotting, Western, Bone Morphogenetic Protein Receptors, Type I, Cell Line, Cell Nucleus, Cloning, Molecular, DNA Mutational Analysis, DNA, Complementary, DNA-Binding Proteins, Genes, Reporter, Homeodomain Proteins, Humans, Immunoprecipitation, Microscopy, Fluorescence, Mutagenesis, Site-Directed, Mutation, Proline, Protein Binding, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, RNA Splicing, RNA-Binding Proteins, Receptors, Growth Factor, Saccharomyces cerevisiae, Signal Transduction, Tissue Distribution, Transfection, Transforming Growth Factor beta, Two-Hybrid System Techniques
Blotting, Northern, Blotting, Western, Bone Morphogenetic Protein Receptors, Type I, Cell Line, Cell Nucleus, Cloning, Molecular, DNA Mutational Analysis, DNA, Complementary, DNA-Binding Proteins, Genes, Reporter, Homeodomain Proteins, Humans, Immunoprecipitation, Microscopy, Fluorescence, Mutagenesis, Site-Directed, Mutation, Proline, Protein Binding, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, RNA Splicing, RNA-Binding Proteins, Receptors, Growth Factor, Saccharomyces cerevisiae, Signal Transduction, Tissue Distribution, Transfection, Transforming Growth Factor beta, Two-Hybrid System Techniques
Biochem. Biophys. Res. Commun.
Date: Oct. 08, 2004
PubMed ID: 15351706
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