Probing the phosphopeptide specificities of protein tyrosine phosphatases, SH2 and PTB domains with combinatorial library methods

Stefan W. Vetter, Zhong-Yin Zhang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Protein tyrosine phosphatases, SH2 and PTB domains are crucial elements for cellular signal transduction and regulation. Much effort has been directed towards elucidating their specificity in the past decade using a variety of approaches. Combinatorial library methods have contributed significantly to the understanding of substrate and ligand specificity of phosphoprotein recognizing domains. This review gives a brief overview of the structural characteristics of protein tyrosine phosphatases, SH2 and PTB domains and their binding to phosphopeptides. The chemical synthesis of peptides containing phosphotyrosine or phosphotyrosine mimics and the various formats of synthesis and deconvolution of combinatorial libraries are explained in detail. Examples are given as how different combinatorial libraries have been used to study the interaction of phosphopeptides with SH2 domains and phosphatases. The intrinsic advantages and difficulties of library synthesis, screening and deconvolution are pointed out. Finally, some experimental results on the substrate specificity of protein tyrosine phosphatase 1B and the SH2 domain of the adaptor protein Grb-2 are summarized and discussed.

Original languageEnglish (US)
Pages (from-to)365-397
Number of pages33
JournalCurrent Protein and Peptide Science
Volume3
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

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Phosphopeptides
Protein Tyrosine Phosphatases
src Homology Domains
Phosphotyrosine
Deconvolution
Substrate Specificity
Non-Receptor Type 1 Protein Tyrosine Phosphatase
Signal transduction
Phosphoproteins
Substrates
Phosphoric Monoester Hydrolases
Screening
Ligands
Signal Transduction
Peptides
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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