Substrate specificity of protein tyrosine phosphatase: differential behavior of SHP-1 and SHP-2 towards signal regulation protein SIRPalpha1

J Cell Biochem. 2002;84(4):840-6. doi: 10.1002/jcb.10090.

Abstract

The substrate specificity of catalytic domains and the activation of full length protein tyrosine phosphatases, SHP-1 and SHP-2 have been investigated using synthetic phosphotyrosyl peptides derived from SIPRalpha1. We found that the catalytic domains of SHP-1 and SHP-2 exhibit different substrate specificity towards a longer trideca-peptide pY(469+3) ((-7)RPEDTLTpYADLDM(+5)) and not to the shorter decapeptide pY(469) ((-5)EDTLTpYADLD(+4)), the former being the substrate of SHP-2 only. Furthermore, the activation of full-length SHP-1 and not the SHP-2 by the deca/trideca-peptides suggested SIRPalpha 1 to be possibly acting as both an upstream activator and a substrate for SHP-1, and merely as the downstream substrate for SHP-2 in signaling events.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Differentiation*
  • Catalytic Domain / physiology
  • Enzyme Activation
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Kinetics
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism*
  • Neural Cell Adhesion Molecule L1*
  • Neural Cell Adhesion Molecules / chemistry
  • Neural Cell Adhesion Molecules / metabolism*
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / isolation & purification
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptors, Immunologic*
  • Substrate Specificity

Substances

  • Antigens, Differentiation
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules
  • Oligopeptides
  • Receptors, Immunologic
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases