The protein-tyrosine phosphatase SHP-1 binds to and dephosphorylates p120 catenin

A prominent tyrosine-phosphorylated protein of similar to 100 kDa (designat ed pp100) in epidermal growth factor (EGF)-stimulated A431 cells was found to be a main interaction partner of the protein-tyrosine phosphatase SHP-1 in pull-down experiments with a glutathione S-transferase-SHP-1 fusion prot ein. Binding was largely mediated by the N-terminal SH2 domain of SHP-1 and apparently direct and independent from the previously described associatio n of SHP-1 with the activated EGF receptor. pp100 was partially purified an d identified by mass spectrometric analysis of tryptic fragments, partial a mino acid sequencing, and use of authentic antibodies as the 3A isoform of the Armadillo repeat protein superfamily member p120 catenin (p120(ctn)). D ifferent p120(ctn) isoforms expressed in human embryonal kidney 293 cells, exhibited differential binding to SHP-1 that correlated partly with the ext ent of EGF-dependent p120(ctn) tyrosine phosphorylation. Despite strong pho sphorylation, p120(ctn) isoforms 3B and 3AB bound, however, less readily to SHP-1. SHP-1 associated transiently with p120(ctn) in EGF-stimulated A431 cells stably transfected with a tetracycline-responsive SHP-1 expression co nstruct, and p120(ctn) exhibited elevated phosphorylation upon a tetracycli ne-mediated decrease in the SHP-1 level. Functions of p120(ctn), which are regulated by tyrosine phosphorylation, may be modulated by the described SH P-1-p120(ctn) interaction.