Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins.
An emerging theme in transforming growth factor-ss (TGF-ss) signalling is the association of the Smad proteins with diverse groups of transcriptional regulatory proteins. Several Smad cofactors have been identified to date but the diversity of TGF-ss effects on gene transcription suggests that interactions with other co-regulators must occur. In these ... studies we addressed the possible interaction of Smad proteins with the myocyte enhancer-binding factor 2 (MEF2) transcriptional regulators. Our studies indicate that Smad2 and 4 (Smad2/4) complexes cooperate with MEF2 regulatory proteins in a GAL4-based one-hybrid reporter gene assay. We have also observed in vivo interactions between Smad2 and MEF2A using co-immunoprecipitation assays. This interaction is confirmed by glutathione S:-transferase pull-down analysis. Immunofluorescence studies in C2C12 myotubes show that Smad2 and MEF2A co-localise in the nucleus of multinuclear myotubes during differentiation. Interestingly, phospho-acceptor site mutations of MEF2 that render it unresponsive to p38 MAP kinase signalling abrogate the cooperativity with the Smads suggesting that p38 MAP Kinase-catalysed phosphorylation of MEF2 is a prerequisite for the Smad-MEF2 interaction. Thus, the association between Smad2 and MEF2A may subserve a physical link between TGF-ss signalling and a diverse array of genes controlled by the MEF2 cis element.
Mesh Terms:
Animals, Binding Sites, COS Cells, Cell Line, Cell Nucleus, Cytoplasm, DNA, Recombinant, DNA-Binding Proteins, Mitogen-Activated Protein Kinases, Myogenic Regulatory Factors, Phosphorylation, Plasmids, Protein Binding, Receptors, Transforming Growth Factor beta, Smad2 Protein, Trans-Activators, Transcription Factors, Transcriptional Activation, Transfection, Transforming Growth Factor beta, p38 Mitogen-Activated Protein Kinases
Animals, Binding Sites, COS Cells, Cell Line, Cell Nucleus, Cytoplasm, DNA, Recombinant, DNA-Binding Proteins, Mitogen-Activated Protein Kinases, Myogenic Regulatory Factors, Phosphorylation, Plasmids, Protein Binding, Receptors, Transforming Growth Factor beta, Smad2 Protein, Trans-Activators, Transcription Factors, Transcriptional Activation, Transfection, Transforming Growth Factor beta, p38 Mitogen-Activated Protein Kinases
Nucleic Acids Res.
Date: Feb. 01, 2001
PubMed ID: 11160896
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