cAMP induces dissociation of inactive PKA tetramers PathwayStep2079 Inactive catalytic PP2B is activated by the binding of calmodulin DARPP-32 is dephosphorylated on Thr34 by PP2B DARPP-32 is dephosphorylated on Thr75 by PP2A cAMP hydrolysis by PDE 4 PKA phosphorylates PDE4B DARPP-32 phosphorylated on T34 binds to PP1, inhibiting its function PKA phosphorylates DARPP-32 on Thr34 DARPP-32 phosphorylated on Thr75 binds to PKA, inhibiting its function CDK5 phosphorylates DARPP-32 on Thr75 PathwayStep5812 PathwayStep5816 PathwayStep5815 PathwayStep5814 PathwayStep5813 PathwayStep5819 PathwayStep5818 PathwayStep5817 PathwayStep5820 DARPP-32 events Authored: Le Novere, N, Jassal, B, 2004-03-31 12:22:05 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. Edited: Jassal, B, 2008-11-06 10:17:49 Pubmed14744247 Pubmed2908293 Reactome Database ID Release 43180024 Reactome, http://www.reactome.org ReactomeREACT_15334 Reviewed: Castagnoli, L, 2008-11-06 12:55:54