Reactome: A Curated Pathway Database

DARPP-32 events (R-HSA-180024) [Homo sapiens]


Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32), was identified as a major target for dopamine and protein kinase A (PKA) in striatum. Recent advances now indicate that regulation DARPP-32 phosphorylation provides a mechanism for integrating information arriving at dopaminoceptive neurons, in multiple brain regions, via a variety of neurotransmitters, neuromodulators, neuropeptides, and steroid hormones. Activation of PKA or PKG stimulates DARPP-32 phosphorylation at Thr34, converting DARPP-32 into a potent inhibitor of protein phosphatase-1 (PP-1). DARPP-32 is also phosphorylated at Thr75 by Cdk5, converting DARPP-32 into an inhibitor of PKA. Thus, DARPP-32 has the unique property of being a dual-function protein, acting either as an inhibitor of PP-1 or of PKA.

Cross References
Database Identifier
BioModels Database BIOMD0000000152, BIOMD0000000153
Literature References
pubMedId Title Journal Year
14744247 DARPP-32: an integrator of neurotransmission Annu Rev Pharmacol Toxicol 2004
2908293 Neuronal phosphoproteins. Mediators of signal transduction Mol Neurobiol 1987