1 research outputs found
Specificity Profiling of Protein Phosphatases toward Phosphoseryl and Phosphothreonyl Peptides
A combinatorial
library method was developed to systematically
profile the substrate specificity of protein phosphatases toward phosphoseryl
(pS) and phosphothreonyl (pT) peptides. Application of this method
and a previously reported phosphotyrosyl (pY) library screening technique
to dual-specificity phosphatase (DUSP) VH1 of vaccinia virus revealed
that VH1 is highly active toward both pS/pT and pY peptides. VH1 exhibits
different and more stringent sequence specificity toward pS/pT than
pY substrates. Unlike previously characterized protein tyrosine phosphatases
(PTPs), the activity and specificity of VH1 are primarily determined
by the amino acid residues C-terminal to the pS, pT, or pY residue.
In contrast, the mammalian VH1-related (VHR) DUSP has intrinsically
low catalytic activity toward pS and pT substrates, suggesting that
its primary physiological function is to dephosphorylate pY residues
in substrate proteins. This method is applicable to other DUSPs and
protein-serine/threonine phosphatases, and the substrate specificity
data will be useful for identifying the physiological substrates of
these enzymes