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Protein phosphatase inhibitor 1/DARPP-32 This family consists of several mammalian protein phosphatase inhibitor 1 (IPP-1) and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) proteins. Protein phosphatase inhibitor-1 is involved in signal transduction and is an endogenous inhibitor of protein phosphatase-1. It has been demonstrated that DARPP-32, if phosphorylated, can inhibit protein-phosphatase-1. DARPP-32 has a key role in many neurotransmitter pathways throughout the brain and has been shown to be involved in controlling receptors, ion channels and other physiological factors including the brain's response to drugs of abuse, such as cocaine, opiates and nicotine. DARPP-32 is reciprocally regulated by the two neurotransmitters that are most often implicated in schizophrenia - dopamine and glutamate. Dopamine activates DARPP-32 through the D1 receptor pathway and disables DARPP-32 through the D2 receptor. Glutamate, acting through the N-methyl-d-aspartate receptor, renders DARPP-32 inactive. A mutant form of DARPP-32 has been linked with gastric cancers. |
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