cAMP Regulated Phosphoprotein 21kDa (ARPP21)

The deduced 89-amino acid ARPP21 protein is 89% identical to the rat and cow proteins. Northern blot analysis detected a 3.0-kb transcript. In situ hybridization analysis revealed expression of ARPP16/19, DARPP32, and ARPP21, with variable intensity, in caudate nucleus, putamen, nucleus accumbens, cerebellar cortex, and neocortex.G protein-coupled receptor (GPCR)-dependent activation of protein kinase A (PKA) led to phosphorylation of RCS at serine-55 and increased its binding to calmodulin. Phospho-RCS acted as a competitive inhibitor of calmodulin-dependent enzymes, including protein phosphatase 2B (PP2B). Increasing RCS phosphorylation blocked GPCR- and PP2B-mediated suppression of L-type calcium currents in striatal neurons. Conversely, genetic deletion of RCS significantly increased this modulation.