PHOSPHOTYROSINE-INDEPENDENT BINDING OF SHC TO THE NPLH SEQUENCE OF MURINE PROTEIN-TYROSINE PHOSPHATASE-PEST - EVIDENCE FOR EXTENDED PHOSPHOTYROSINE BINDING PHOSPHOTYROSINE INTERACTION DOMAIN RECOGNITION SPECIFICITY

The phosphotyrosine binding (PTB) or phosphotyrosine interaction (PI) domain of the proto-oncoprotein p52(SHC) binds to an NPXpY consensus s equence found in several growth factor receptors (Kavanaugh, W. M., Tu rck, C. W., and Williams, L. T. (1994) Science 268, 1177-1179), The am ino terminal region of p52(SHC), which includes the PTB/PI domain, has been previously shown to associate with protein-tyrosine phosphatase- PEST (PTP-PEST) in vivo (Habib, T., Herrera, R., and Decker, S. J. (19 94) J. Biol. Chem. 269, 25243-25246). We report here the detailed mapp ing of this interaction in a murine context using glutathione S-transf erase fusion protein binding studies and peptide competition assays. W e show that the interaction between murine SHC and murine PTP-PEST is mediated through the PTB/PI domain of murine SHC and an NPLH sequence found in the carboxyl terminus of murine PTP-PEST. Since this interact ion is not dependent on the presence of a tyrosine-phosphorylated resi due in the target sequence, this reveals that the PTB/PI domain of SHC can recognize both tyrosine-phosphorylated sequences and non-tyrosine -based recognition motifs.