One of the central questions in studying protein-tyrosine phosphatases (PTPaaes) is how they distinguish the diversity of substrates that they encounter in the cell. A detailed understanding of PTPase substrate specificity is crucial for the design and development of potent and selective inhibitors which may serve as new tools for studying signal transduction. Our studies using synthetic phosphopeptides have demonstrated that PTPases are sensitive to the amino acid sequence that encompasses the phosphotyrosine moiety. We show that in addition to aryl phosphates, PTPases can also dephosphorylate a variety of aliphatic phosphates. Several potent low molecular weight nonpeptide substrates have been identified. In contrast to the currently held belief that phosphotyrosine is absolutely essential for PTPase recognition of protein- and peptide-based substrates, we have found that PTPases will hydrolyze a variety of both aromatic and aliphatic phosphates fused to an active site-directed peptide. A comparative anlysis of the active site specificity of PTPases reveals key differences in the ability of individual enzymes to tolerate specific structural elements. Clearly, any observed differences should prove useful in the design of PTPase-specific inhibitors.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology