DIMERIZATION-INDUCED INHIBITION OF RECEPTOR PROTEIN-TYROSINE-PHOSPHATASE FUNCTION THROUGH AN INHIBITORY WEDGE

The function and regulation of the receptorlike transmembrane protein tyrosine phosphatases (RPTPs) are not well understood. Ligand-induced dimerization inhibited the function of the epidermal growth factor rec eptor (EGFR)-RPTP CD45 chimera (EGFR-CD45) in T cell signal transducti on. Properties of mutated EGFR-CD45 chimeras supported a general model for the regulation of RPTPs, derived from the crystal structure of th e RPTP alpha membrane-proximal phosphatase domain, The phosphatase dom ain apparently forms a symmetrical dimer in which the catalytic site o f one molecule is blocked by specific contacts with a wedge from the o ther.