Format

Send to

Choose Destination
FEBS Lett. 2007 Oct 2;581(24):4767-72. Epub 2007 Sep 11.

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

Author information

1
Institute for Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Abstract

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.

PMID:
17880946
DOI:
10.1016/j.febslet.2007.08.077
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center