The comparative substrate specificity of protein-tyrosine phosphatases

Zhong-Yin Zhang, L. Chen, D. Dunn, J. Montserat, D. S. Lawrence

Research output: Contribution to journalArticle

Abstract

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 languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996
Externally publishedYes

Fingerprint

protein-tyrosine-phosphatase
Protein Tyrosine Phosphatases
substrate specificity
Substrate Specificity
phosphates
active sites
Phosphotyrosine
Phosphates
Substrates
peptides
Catalytic Domain
Phosphopeptides
Signal transduction
Peptides
aromatic compounds
signal transduction
amino acid sequences
molecular weight
Amino Acid Sequence
Signal Transduction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Zhang, Z-Y., Chen, L., Dunn, D., Montserat, J., & Lawrence, D. S. (1996). The comparative substrate specificity of protein-tyrosine phosphatases. FASEB Journal, 10(6).

The comparative substrate specificity of protein-tyrosine phosphatases. / Zhang, Zhong-Yin; Chen, L.; Dunn, D.; Montserat, J.; Lawrence, D. S.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Zhang, Z-Y, Chen, L, Dunn, D, Montserat, J & Lawrence, DS 1996, 'The comparative substrate specificity of protein-tyrosine phosphatases', FASEB Journal, vol. 10, no. 6.
Zhang, Zhong-Yin ; Chen, L. ; Dunn, D. ; Montserat, J. ; Lawrence, D. S. / The comparative substrate specificity of protein-tyrosine phosphatases. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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