Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains.

Abstract

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.

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@article{Bedford2000ArginineMI, title={Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains.}, author={Marc T Bedford and Arthur D. Frankel and Michael B. Yaffe and Stephen Clarke and Philip Leder and St{\'e}phane Richard}, journal={The Journal of biological chemistry}, year={2000}, volume={275 21}, pages={16030-6} }