Ca, cAMP & Lipid Signaling

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).

1. Nishi, A. et al. (1997) J. Neurosci. 17, 8147-8155.
2. Bibb, J.A. et al. (1999) Nature 402, 669-671.
3. Fienberg, A.A. et al. (1998) Science 281, 838-842.

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DARPP-32 Blocking Peptide

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