A PROTEIN-TYROSINE-PHOSPHATASE EXPRESSED WITHIN DOPAMINOCEPTIVE NEURONS OF THE BASAL GANGLIA AND RELATED STRUCTURES

Immunocytochemical and biochemical studies were conducted to character ize a brain-specific protein tyrosine phosphatase, designated STEP for striatal enriched phosphatase. STEP immunoreactivity was most intense in select regions of the CNS receiving a dopaminergic input, and was localized to cell bodies, dendrites, and axonal processes. Western blo t analyses of rat brain homogenates revealed a triplet of polypeptides with relative mobilities (M(r)) of 46 kDa, 37 kDa, and 33 kDa enriche d within the striatum. Phase separation of protein homogenates by Trit on X-114 extraction indicated that this triplet was enriched in solubl e but not membrane fractions. Affinity-purified STEP fusion protein ex hibited phosphatase activity while a mutated form of the STEP fusion p rotein (Cys300Ser) showed no demonstrable phosphatase activity.