IDENTIFICATION OF AN AMINO-TERMINAL SUBSTRATE-BINDING DOMAIN IN THE YERSINIA TYROSINE PHOSPHATASE THAT IS REQUIRED FOR EFFICIENT RECOGNITION OF FOCAL ADHESION TARGETS

YopH is a protein tyrosine phosphatase (PTP) that is delivered into ho st mammalian cells via a type III secretion pathway in pathogenic Yers inia species. Although YopH is a highly active PTP, it preferentially targets a subset of tyrosine-phosphorylated proteins in host cells, in cluding p130(Cas). Previous in vitro studies have indicated that the c arboxy-terminal PTP domain contributes specificity to the interaction of YopH with substrates. However, it is not known if the PTP domain is sufficient for substrate recognition by YopH. Here, we have identifie d paxillin as an additional substrate of YopH in HeLa cells. In additi on, we have identified a domain in the amino-terminal region of YopH t hat binds to both p130(Cas) and paxillin and is required for the effic ient recognition of substrates by the wild-type enzyme. This 'substrat e-binding' domain exhibits a ligand specificity that is similar to tha t of the Crk Src homology 2 (SH2) domain, and it binds substrates dire ctly in a phosphotyrosine-dependent manner. The substrate-binding doma in of YopH may represent a novel type of protein-protein interaction m odule, as it lacks significant sequence similarity with any known SH2 or phosphotyrosine-binding (PTB) domain.