Arginine Methylation Inhibits the Binding of Proline-rich Ligands to Src Homology 3, but Not WW, Domains
Copyright policy )Arginine Methylation Inhibits the Binding of Proline-rich Ligands to Src Homology 3, but Not WW, Domains
Src homology 3 (SH3) and WW domains are known to associate with proline-rich motifs within their respective ligands. Here we demonstrate that the proposed adapter protein for Src kinases, Sam68, is a ligand whose proline-rich motifs interact with the SH3 domains of p59(fyn) and phospholipase Cgamma-1 as well as with the WW domains of FBP30 and FBP21. These proline-rich motifs, in turn, are flanked by RG repeats that represent targets for the type I protein arginine N-methyltransferase. The asymmetrical dimethylation of arginine residues within these RG repeats dramatically reduces the binding of the SH3 domains of p59(fyn) and phospholipase Cgamma-1, but has no effect on their binding to the WW domain of FBP30. These results suggest that protein arginine methylation can selectively modulate certain protein-protein interactions and that mechanisms exist for the irreversible regulation of SH3 domain-mediated interactions.
- Harvard University United States
- Howard Hughes Medical Institute United States
- Beth Israel Deaconess Medical Center United States
- McGill University Canada
- University of California, Los Angeles United States
Models, Molecular, Protein-Arginine N-Methyltransferases, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Tryptophan, RNA-Binding Proteins, Methyltransferases, Arginine, Ligands, Proto-Oncogene Proteins c-fyn, Methylation, Peptide Fragments, src Homology Domains, Proto-Oncogene Proteins, Yeasts, Amino Acid Sequence, Carrier Proteins, Protein Binding
Models, Molecular, Protein-Arginine N-Methyltransferases, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Tryptophan, RNA-Binding Proteins, Methyltransferases, Arginine, Ligands, Proto-Oncogene Proteins c-fyn, Methylation, Peptide Fragments, src Homology Domains, Proto-Oncogene Proteins, Yeasts, Amino Acid Sequence, Carrier Proteins, Protein Binding
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