Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1

UMMS Affiliation

Program in Molecular Medicine; Department of Pharmacology and Molecular Toxicology

Publication Date


Document Type



Animals; Binding Sites; Crystallography, X-Ray; Hydrogen Bonding; Intracellular Signaling Peptides and Proteins; Kinetics; Models, Molecular; Peptides; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases; Sequence Homology, Amino Acid; Software; Substrate Specificity


Life Sciences | Medicine and Health Sciences


The substrate specificity of the catalytic domain of SHP-1, an important regulator in the proliferation and development of hematopoietic cells, is critical for understanding the physiological functions of SHP-1. Here we report the crystal structures of the catalytic domain of SHP-1 complexed with two peptide substrates derived from SIRPalpha, a member of the signal-regulatory proteins. We show that the variable beta5-loop-beta6 motif confers SHP-1 substrate specificity at the P-4 and further N-terminal subpockets. We also observe a novel residue shift at P-2, the highly conserved subpocket in protein- tyrosine phosphatases. Our observations provide new insight into the substrate specificity of SHP-1.


J Biol Chem. 2000 Feb 11;275(6):4066-71.

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to Article in PubMed

PubMed ID