Phospho-DARPP-32 (Ser97) (D11A5) Rabbit mAb #3401

DARPP-32 (dopamine and cyclic AMP-regulated phosphoprotein, relative molecular mass 32,000) is a cytosolic protein highly enriched in medium-sized spiny neurons of the neostriatum (1). It is a bifunctional signaling molecule that controls serine/threonine kinase and serine/threonine phosphatase activity (2). Dopamine stimulates phosphorylation of DARPP-32 through D1 receptors and activation of PKA. PKA phosphorylation of DARPP-32 at Thr34 converts it into an inhibitor of protein phosphatase 1 (1). DARPP-32 is converted into an inhibitor of PKA when phosphorylated at Thr75 by cyclin-dependent kinase 5 (CDK5) (2). Mice containing a targeted deletion of the DARPP-32 gene exhibit an altered biochemical, electrophysiological, and behavioral phenotype (3).
Drugs of abuse such as cocaine and food reinforcement learning activate the dopamine D1 receptor-signaling cascade. The downstream effector DARPP-32 is dephosphorylated at Ser97 inhibiting its nuclear export. This enables DARPP-32 to function as an inhibitor of protein phosphatase-1, increasing phosphorylation of histone H3 at Ser10. Knock-in mice bearing a DARPP-32 Ser97 to Ala (S97A) mutation demonstrate changed behavioral effects to drugs of abuse and a decreased motivation for food (4).