Phosphotyrosine-independent binding of SHC to the NPLH sequence of murine protein-tyrosine phosphatase-PEST. Evidence for extended phosphotyrosine binding/phosphotyrosine interaction domain recognition specificity

J Biol Chem. 1996 Apr 5;271(14):8424-9. doi: 10.1074/jbc.271.14.8424.

Abstract

The phosphotyrosine binding (PTB) or phosphotyrosine interaction (PI) domain of the proto-oncoprotein p52SHC binds to an NPXpY consensus sequence found in several growth factor receptors (Kavanaugh, W. M., Turck, C. W., and Williams, L. T. (1994) Science 268, 1177-1179). The amino-terminal region of p52SHC, which includes the PTB/PI domain, has been previously shown to associate with protein-tyrosine phosphatase-PEST (PTP-PEST) in vivo (Habib, T. , Herrera, R., and Decker, S. J. (1994) J. Biol. Chem. 269, 25243-25246). We report here the detailed mapping of this interaction in a murine context using glutathione S-transferase fusion protein binding studies and peptide competition assays. We show that the interaction between murine SHC and murine PTP-PEST is mediated through the PTB/PI domain of murine SHC and an NPLH sequence found in the carboxyl terminus of murine PTP-PEST. Since this interaction is not dependent on the presence of a tyrosine-phosphorylated residue in the target sequence, this reveals that the PTB/PI domain of SHC can recognize both tyrosine-phosphorylated sequences and non-tyrosine-based recognition motifs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Animals
  • Histidine / chemistry
  • Mice
  • Molecular Sequence Data
  • Peptides / chemistry
  • Phosphotyrosine / chemistry
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases / metabolism*
  • Proteins / metabolism*
  • Recombinant Proteins
  • Shc Signaling Adaptor Proteins
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Structure-Activity Relationship

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Peptides
  • Proteins
  • Recombinant Proteins
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Phosphotyrosine
  • Histidine
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Protein Tyrosine Phosphatases
  • Ptpn12 protein, mouse