An alternative to SH2 domains for binding tyrosine-phosphorylated proteins

Science. 1994 Dec 16;266(5192):1862-5. doi: 10.1126/science.7527937.

Abstract

Src homology 2 (SH2) domains bind specifically to tyrosine-phosphorylated proteins that participate in signaling by growth factors and oncogenes. A protein domain was identified that bound specifically to the tyrosine-phosphorylated form of its target protein but differs from known SH2 sequences. Phosphotyrosine-binding (PTB) domains were found in two proteins: SHC, a protein implicated in signaling through Ras; and SCK, encoded by a previously uncharacterized gene. The PTB domain of SHC specifically bound to a tyrosine-phosphorylated 145-kilodalton protein. PTB domains are an alternative to SH2 domains for specifically recruiting tyrosine-phosphorylated proteins into signaling complexes and are likely to take part in signaling by many growth factors.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Humans
  • Mice
  • Molecular Sequence Data
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotyrosine
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Binding
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / chemistry
  • Proteins / metabolism*
  • Shc Signaling Adaptor Proteins
  • Signal Transduction*
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Phosphoproteins
  • Platelet-Derived Growth Factor
  • Proteins
  • SHC1 protein, human
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Phosphotyrosine
  • Tyrosine
  • Protein-Tyrosine Kinases