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Suppressor of T‐cell receptor signalling 1 and 2 differentially regulate endocytosis and signalling of receptor tyrosine kinases
Author(s) -
Raguz Josipa,
Wagner Sebastian,
Dikic Ivan,
Hoeller Daniela
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.08.077
Subject(s) - endocytosis , microbiology and biotechnology , receptor tyrosine kinase , receptor protein tyrosine kinases , protein tyrosine phosphatase , receptor , tyrosine kinase , biology , signalling , proto oncogene tyrosine protein kinase src , ror1 , kinase , sh3 domain , receptor mediated endocytosis , chemistry , signal transduction , biochemistry , platelet derived growth factor receptor , growth factor
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.