Protein Phosphatase 1, Regulatory Subunit 1B (PPP1R1B), also known as Dopamine- and Cyclic AMP-Regulated Phosphoprotein 32 kDa (DARPP-32), is an inhibitor of protein phosphatase-1(PP1) and protein kinase A (PKA). The addition of phosphate groups by kinases and their removal by phosphatases is an essential mechanism to regulate the activity of a signaling molecule – with the phosphorylated state generally “on” and the dephosphorylated state generally “off.” Stimulation of dopamine D1 receptors increases DARPP-32 phosphatase inhibition, while stimulation of NMDA receptors reduces phosphatase inhibition. In addition, DARPP-32 can decrease phosphorylation by directly inhibiting protein kinase A. Because it integrates signaling from several key pathways and broadly modulates phosphorylation, DARPP-32 mutations can interfere with normal dopamine signaling in midbrain neurons. DARPP-32 appears critical to motivated behavior, working memory, and reward-related learning, and has been implicated in schizophrenia, Parkinson disease, alcoholism, drug abuse, and pathological gambling.

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