title: DARPP-32 and modulation of cAMP signaling: involvement in motor control and levodopa-induced dyskinesia.
abstract: The dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) is abundantly expressed in the medium spiny neurons of the striatum. Phosphorylation catalysed by cAMP-dependent protein kinase (PKA) converts DARPP-32 into an inhibitor of protein phosphatase-1. In contrast, phosphorylation catalysed by cyclin dependent kinase-5 on Thr75 converts DARPP-32 into an inhibitor of PKA. Changes in the state of phosphorylation of DARPP-32 reinforce the behavioral effects produced by stimulation or inhibition of the cAMP pathway. Dopamine, via D(1) receptors, and adenosine, via A(2A) receptors, affect motor behavior by acting on medium spiny neurons, via G(olf) mediated stimulation of the cAMP signaling cascade. The involvement of DARPP-32 in dopamine and adenosine transmission and the possible role played by abnormal regulation of DARPP-32 phosphorylation in levodopa-induced dyskinesia are discussed.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, S-17177 Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Håkansson
authors.forename: Maria
authors.initials: M
authors.lastname: Lindskog
authors.forename: Laura
authors.initials: L
authors.lastname: Pozzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Usiello
authors.forename: Gilberto
authors.initials: G
authors.lastname: Fisone
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000633:toxicity; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D007980:Levodopa; D000242:Cyclic AMP