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

Product Usage Information

Storage

Specificity / Sensitivity

Species Reactivity:

Human, Mouse, Rat

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser102 of human DARPP-32 protein (equivalent to Ser97 of mouse DARPP-32 protein).

Background

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).