Suppressor of T-cell receptor signalling 1 and 2 differentially regulate endocytosis and signalling of receptor tyrosine kinases

FEBS Lett. 2007 Oct 2;581(24):4767-72. doi: 10.1016/j.febslet.2007.08.077. Epub 2007 Sep 11.


Suppressor of T-cell receptor signalling 1 and 2 (Sts-1 and 2) negatively regulate the endocytosis of receptor tyrosine kinases. The UBA domain of Sts-2 and SH3-dependent Cbl-binding are required for this function. Sts-1 and -2 also possess a PGM domain, which was recently reported to exhibit tyrosine phosphatase activity. Here, we demonstrate that the PGM of Sts-1, but not of Sts-2, dephosphorylates the EGFR at multiple tyrosines thereby terminating its signalling and endocytosis. In contrast to Sts-2 the UBA of Sts-1 did not contribute significantly to receptor stabilization. Thus, although Sts-1 and Sts-2 are structurally highly homologous and both inhibit ligand-induced EGFR degradation, their mechanisms of action differ significantly. As a consequence, Sts-1-containing receptor complexes are inactive, whereas Sts-2-containing complexes are signalling competent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Conserved Sequence
  • Down-Regulation
  • Endocytosis*
  • ErbB Receptors / metabolism*
  • Humans
  • Molecular Sequence Data
  • Phosphoric Monoester Hydrolases / metabolism
  • Sequence Alignment
  • Signal Transduction*


  • Adaptor Proteins, Signal Transducing
  • ErbB Receptors
  • Phosphoric Monoester Hydrolases