Interaction of the adaptor protein Shc and the adhesion molecule cadherin

J Biol Chem. 1997 May 23;272(21):13463-6. doi: 10.1074/jbc.272.21.13463.


In mitogenic signaling pathways, Shc participates in the growth factor activation of Ras by interacting with activated receptors and/or the Grb-2.Sos complex. Using several experimental approaches we demonstrate that Shc, through its SH2 domain, forms a complex with the cytoplasmic domain of cadherin, a transmembrane protein involved in the Ca2+-dependent regulation of cell-cell adhesion. This interaction is demonstrated in a yeast two-hybrid assay, by co-precipitation from mammalian cells, and by direct biochemical analysis in vitro. The Shc-cadherin association is phosphotyrosine-dependent and is abrogated by addition of epidermal growth factor to A-431 cells maintained in Ca2+-free medium, a condition that promotes changes in cell shape. Shc may therefore participate in the control of cell-cell adhesion as well as mitogenic signaling through Ras.

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
  • Cadherins / metabolism*
  • Cell Adhesion
  • Cell Size
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Genetic Techniques
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Proteins / metabolism*
  • Shc Signaling Adaptor Proteins
  • Signal Transduction*
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Tyrosine / metabolism
  • Vanadates / pharmacology
  • src Homology Domains*


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Cadherins
  • Enzyme Inhibitors
  • Proteins
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • pervanadate
  • Vanadates
  • Tyrosine
  • Epidermal Growth Factor
  • Protein Tyrosine Phosphatases