dopamine and camp regulated phosphoprotein 32


Summary: A phosphoprotein that was initially identified as a major target of DOPAMINE activated ADENYLYL CYCLASE in the CORPUS STRIATUM. It regulates the activities of PROTEIN PHOSPHATASE-1 and PROTEIN KINASE A, and it is a key mediator of the biochemical, electrophysiological, transcriptional, and behavioral effects of DOPAMINE.

Top Publications

  1. Belkhiri A, Dar A, Peng D, Razvi M, Rinehart C, Arteaga C, et al. Expression of t-DARPP mediates trastuzumab resistance in breast cancer cells. Clin Cancer Res. 2008;14:4564-71 pubmed publisher
    ..This association may play a role in regulating ERBB2 protein in trastuzumab-resistant cells. We conclude that t-DARPP is a novel molecular target that can mediate the therapeutic resistance to trastuzumab in breast cancer cells. ..
  2. Gerfen C, Paletzki R, Worley P. Differences between dorsal and ventral striatum in Drd1a dopamine receptor coupling of dopamine- and cAMP-regulated phosphoprotein-32 to activation of extracellular signal-regulated kinase. J Neurosci. 2008;28:7113-20 pubmed publisher
    ..These findings indicate that Drd1a sensitization relevant for PD occurs by a novel mechanism that does not require DARPP-32. ..
  3. Logue S, Grauer S, Paulsen J, Graf R, Taylor N, Sung M, et al. The orphan GPCR, GPR88, modulates function of the striatal dopamine system: a possible therapeutic target for psychiatric disorders?. Mol Cell Neurosci. 2009;42:438-47 pubmed publisher
    ..Antipsychotic administration to Gpr88KOs normalized the PPI deficit and blocked AICS. The modulatory role of Gpr88 in striatal dopamine function suggests it may be a new target for treatments for psychiatric disorders. ..
  4. Danielli B, Scheggi S, Grappi S, Marchese G, De Montis M, Tagliamonte A, et al. Modifications in DARPP-32 phosphorylation pattern after repeated palatable food consumption undergo rapid habituation in the nucleus accumbens shell of non-food-deprived rats. J Neurochem. 2010;112:531-41 pubmed publisher
    ..Thus, dopamine D(1) receptor stimulation plays a role in the development of habituation. ..
  5. Napolitano F, Bonito Oliva A, Federici M, Carta M, Errico F, Magara S, et al. Role of aberrant striatal dopamine D1 receptor/cAMP/protein kinase A/DARPP32 signaling in the paradoxical calming effect of amphetamine. J Neurosci. 2010;30:11043-56 pubmed publisher
  6. Frank M, Doll B, Oas Terpstra J, Moreno F. Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation. Nat Neurosci. 2009;12:1062-8 pubmed publisher
    ..Quantitative model fits reveal that genetic factors modulate independent parameters of a reinforcement learning system. ..
  7. Kornum B, Stott S, Mattsson B, Wisman L, Ettrup A, Hermening S, et al. Adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain. Exp Neurol. 2010;222:70-85 pubmed publisher
    ..Finally, we generated an atlas of the Göttingen minipig brain for guiding future studies in this large animal species. ..
  8. Meyer Lindenberg A. Neural connectivity as an intermediate phenotype: brain networks under genetic control. Hum Brain Mapp. 2009;30:1938-46 pubmed publisher
    ..These data provide convergent evidence for genetic control in humans over connectivity systems, whose characterization has promise for identifying neural systems mediating genetic risk for complex human behavior and psychiatric disease. ..
  9. Faideau M, Kim J, Cormier K, Gilmore R, Welch M, Auregan G, et al. In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjects. Hum Mol Genet. 2010;19:3053-67 pubmed publisher
    ..These findings suggest that the presence of mHtt in astrocytes alters glial glutamate transport capacity early in the disease process and may contribute to HD pathogenesis. ..

More Information


  1. Weiner J, Sun W, Zhou L, Kreiter C, Jenab S, Quinones Jenab V. PKA-mediated responses in females' estrous cycle affect cocaine-induced responses in dopamine-mediated intracellular cascades. Neuroscience. 2009;161:865-76 pubmed publisher
    ..Taken together, these novel findings suggest that hormonal fluctuations during the estrous cycle may contribute to the previously reported sex differences in the PKA pathway and in behavioral responses to cocaine. ..
  2. Reuter M, Weber B, Fiebach C, Elger C, Montag C. The biological basis of anger: associations with the gene coding for DARPP-32 (PPP1R1B) and with amygdala volume. Behav Brain Res. 2009;202:179-83 pubmed publisher
    ..The present findings yield genetic evidence for the importance of dopaminergic signal transduction for the personality trait of ANGER. In addition volumetric MRI data support the role of the amygdala for the processing of anger. ..
  3. Salvatore M, Gerhardt G, Dayton R, Klein R, Stanford J. Bilateral effects of unilateral GDNF administration on dopamine- and GABA-regulating proteins in the rat nigrostriatal system. Exp Neurol. 2009;219:197-207 pubmed publisher
    ..Enhanced nigrostriatal excitability and DA release by GDNF may trigger these bilateral effects. ..
  4. Frye C, Walf A. Infusions of anti-sense oligonucleotides for DARPP-32 to the ventral tegmental area reduce effects of progesterone- and a dopamine type 1-like receptor agonist to facilitate lordosis. Behav Brain Res. 2010;206:286-92 pubmed publisher
    ..Together, these findings suggest that, in the midbrain VTA, P4's actions to facilitate sexual behavior of female rodents, involving D1 receptors, may require DARPP-32. ..
  5. Roybon L, Mastracci T, Ribeiro D, Sussel L, Brundin P, Li J. GABAergic differentiation induced by Mash1 is compromised by the bHLH proteins Neurogenin2, NeuroD1, and NeuroD2. Cereb Cortex. 2010;20:1234-44 pubmed publisher
    ..Collectively, our results define the compensatory and cross-regulatory mechanisms that exist among basic helix-loop-helix transcription factors during neuronal fate specification. ..
  6. Lebel M, Chagniel L, Bureau G, Cyr M. Striatal inhibition of PKA prevents levodopa-induced behavioural and molecular changes in the hemiparkinsonian rat. Neurobiol Dis. 2010;38:59-67 pubmed publisher
  7. Jacobsen J, Bawden C, Rudiger S, McLaughlan C, Reid S, Waldvogel H, et al. An ovine transgenic Huntington's disease model. Hum Mol Genet. 2010;19:1873-82 pubmed publisher
    ..New sequence accession number for ovine HTT mRNA: FJ457100...
  8. Song L, Kong M, Ma Y, Ba M, Liu Z. Inhibitory effect of 8-(3-chlorostryryl) caffeine on levodopa-induced motor fluctuation is associated with intracellular signaling pathway in 6-OHDA-lesioned rats. Brain Res. 2009;1276:171-9 pubmed publisher
    ..Our results indicate that the inhibitory effect of CSC on levodopa-induced motor fluctuation may be associated with the inhibition of Adenosine A(2A) Receptor and downstream DARPP-32 and ERK1/2 signaling pathway. ..
  9. Bryant C, Graham M, Distler M, Munoz M, Li D, Vezina P, et al. A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine. Psychopharmacology (Berl). 2009;203:703-11 pubmed publisher
  10. Hara M, Fukui R, Hieda E, Kuroiwa M, Bateup H, Kano T, et al. Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons. J Neurochem. 2010;113:1046-59 pubmed publisher
    ..alpha(2)-Adrenoceptors may therefore be a therapeutic target for the treatment of Parkinson's disease. ..
  11. Visanji N, Fox S, Johnston T, Reyes G, Millan M, Brotchie J. Dopamine D3 receptor stimulation underlies the development of L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Neurobiol Dis. 2009;35:184-92 pubmed publisher
    ..Our data suggest a role for D3 receptors in the development of LID and suggest that initiating L-DOPA treatment with a D3 antagonist may reduce the development of LID in PD. ..
  12. Sun W, Zhou L, Hazim R, Quinones Jenab V, Jenab S. Effects of acute cocaine on ERK and DARPP-32 phosphorylation pathways in the caudate-putamen of Fischer rats. Brain Res. 2007;1178:12-9 pubmed
    ..The phosphorylation states of these inhibitors of ERK and DARPP-32 proteins may thus contribute to the effects of cocaine on ERK- and DARPP-32-mediated cascades, on gene expression and on behaviors. ..
  13. Meurers B, Dziewczapolski G, Shi T, Bittner A, Kamme F, Shults C. Dopamine depletion induces distinct compensatory gene expression changes in DARPP-32 signal transduction cascades of striatonigral and striatopallidal neurons. J Neurosci. 2009;29:6828-39 pubmed publisher
    ..In addition, the data have potential implications for the symptomatic treatment of the disease...
  14. Guan Q, Liu X, He Y, Jin L, Zhao L. Effect of cdk5 antagonist on L-dopa-induced dyskinesias in a rat model of Parkinson's disease. Int J Neurosci. 2010;120:421-7 pubmed publisher
    ..These findings suggest that up-regulated expression of Cdk5 may compensate the high levels of phosphorylation of DARPP-32 at Thr34 in LID rats. Therefore, modulation of Cdk5 for therapy of human PD should be carefully reconsidered...
  15. Boeck C, Marques V, Valvassori S, Constantino L, Rosa D, Lima F, et al. Early long-term exposure with caffeine induces cross-sensitization to methylphenidate with involvement of DARPP-32 in adulthood of rats. Neurochem Int. 2009;55:318-22 pubmed publisher
    ..However, no alteration caused by these treatments was noted in the hippocampus. In conclusion, chronic caffeine exposure induces likely long-term cross-sensitization to MPH in a DARPP-32-dependent pathway. ..
  16. Sears R, Liu R, Narayanan N, Sharf R, Yeckel M, Laubach M, et al. Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone. J Neurosci. 2010;30:8263-73 pubmed publisher
    ..The current work integrates the hypothalamus into this model, providing biochemical and cellular mechanisms whereby metabolic and limbic signals converge to regulate food intake. ..
  17. Mukherjee K, Peng D, Brifkani Z, Belkhiri A, Pera M, Koyama T, et al. Dopamine and cAMP regulated phosphoprotein MW 32 kDa is overexpressed in early stages of gastric tumorigenesis. Surgery. 2010;148:354-63 pubmed publisher
    ..The ability of DARPP-32 to transform NIH3T3 cells and to regulate AKT and BCL-2 underscores its possible oncogenic potential. ..
  18. Park H, Cui F, Roh J, Jung Y, Kim S, Kim Y, et al. Effects of electroconvulsive shock on the phosphorylation of DARPP-32 in rat striatum. Psychiatry Res. 2009;170:91-5 pubmed publisher
    ..Our findings indicate that ECS increases Thr34 phosphorylation of DARPP-32, and thus inhibits the activity of PP1. ..
  19. Hansen C, Howlin J, Tengholm A, Dyachok O, Vogel W, Nairn A, et al. Wnt-5a-induced phosphorylation of DARPP-32 inhibits breast cancer cell migration in a CREB-dependent manner. J Biol Chem. 2009;284:27533-43 pubmed publisher
  20. Mahajan S, Aalinkeel R, Reynolds J, Nair B, Sykes D, Hu Z, et al. Therapeutic targeting of "DARPP-32": a key signaling molecule in the dopiminergic pathway for the treatment of opiate addiction. Int Rev Neurobiol. 2009;88:199-222 pubmed publisher
    ..These findings have the potential to facilitate the development of DARPP32 siRNA-based therapeutics against drug addiction. ..
  21. Benderska N, Becker K, Girault J, Becker C, Andreadis A, Stamm S. DARPP-32 binds to tra2-beta1 and influences alternative splicing. Biochim Biophys Acta. 2010;1799:448-53 pubmed publisher
    ..DARPP-32 changes the usage of tra2-beta1 dependent alternative exons in a concentration-dependent manner, suggesting that the DARPP-32:tra2-beta1 interaction is a molecular link between signaling pathways and pre-mRNA processing. ..
  22. Rajput P, Kharmate G, Somvanshi R, Kumar U. Colocalization of dopamine receptor subtypes with dopamine and cAMP-regulated phosphoprotein (DARPP-32) in rat brain. Neurosci Res. 2009;65:53-63 pubmed publisher
  23. Bateup H, Santini E, Shen W, Birnbaum S, Valjent E, Surmeier D, et al. Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors. Proc Natl Acad Sci U S A. 2010;107:14845-50 pubmed publisher
    ..These findings provide insight into the selective contributions of the direct and indirect pathways to striatal motor behaviors. ..
  24. Metzler M, Gan L, Mazarei G, Graham R, Liu L, Bissada N, et al. Phosphorylation of huntingtin at Ser421 in YAC128 neurons is associated with protection of YAC128 neurons from NMDA-mediated excitotoxicity and is modulated by PP1 and PP2A. J Neurosci. 2010;30:14318-29 pubmed publisher
  25. Bertran Gonzalez J, Hakansson K, Borgkvist A, Irinopoulou T, Brami Cherrier K, Usiello A, et al. Histone H3 phosphorylation is under the opposite tonic control of dopamine D2 and adenosine A2A receptors in striatopallidal neurons. Neuropsychopharmacology. 2009;34:1710-20 pubmed publisher
    ..Thus, blockade of D2Rs promotes histone H3 phosphorylation through the A2AR-mediated activation of Galpha(olf) and inhibition of protein phosphatase-1 (PP-1) through the PKA-dependent phosphorylation of DARPP-32. ..
  26. Bonoiu A, Mahajan S, Ding H, Roy I, Yong K, Kumar R, et al. Nanotechnology approach for drug addiction therapy: gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons. Proc Natl Acad Sci U S A. 2009;106:5546-50 pubmed publisher
    ..Therefore, these nanoplexes appear to be suited for brain-specific delivery of appropriate siRNA for therapy of drug addiction and other brain diseases. ..
  27. Drouet V, Perrin V, Hassig R, Dufour N, Auregan G, Alves S, et al. Sustained effects of nonallele-specific Huntingtin silencing. Ann Neurol. 2009;65:276-85 pubmed publisher
    ..These data indicate that the coincident silencing of the wild-type and mutant htt may be considered as a therapeutic tool for HD. ..
  28. Zakharova E, Miller J, Unterwald E, Wade D, Izenwasser S. Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats. Neuroscience. 2009;163:890-7 pubmed publisher
  29. Scheggi S, Crociani A, De Montis M, Tagliamonte A, Gambarana C. Dopamine D1 receptor-dependent modifications in the dopamine and cAMP-regulated phosphoprotein of Mr 32 kDa phosphorylation pattern in striatal areas of morphine-sensitized rats. Neuroscience. 2009;163:627-39 pubmed publisher
    ..Since DARPP-32 phosphorylated in Thr75 inhibits cAMP-dependent protein kinase (PKA) activity, the final result is a decrease in the dopamine D(1) receptor-dependent phosphorylation events. ..
  30. Carrera N, Arrojo M, Paz E, Ramos Ríos R, Agra S, Páramo M, et al. Testing the antagonistic pleiotropy model of schizophrenia susceptibility by analysis of DAOA, PPP1R1B, and APOL1 genes. Psychiatry Res. 2010;179:126-9 pubmed publisher
    ..We did not detect evidence of recent natural selection. Furthermore, we did not find significant associations. Thus, these genes do not fit the antagonistic pleiotropy model. ..
  31. Mancuso J, Qian Y, Long C, Wu G, Wensel T. Distribution of RGS9-2 in neurons of the mouse striatum. J Neurochem. 2010;112:651-61 pubmed publisher
    ..An important nuclear function for RGS9-2 seems unlikely. ..
  32. Björk K, Terasmaa A, Sun H, Thorsell A, Sommer W, Heilig M. Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors. Addict Biol. 2010;15:299-303 pubmed publisher
    ..One of these is D2-dependent, while the other is not. These findings illustrate that pharmacology of ethanol reward is likely more complex than that for other addictive drugs. ..
  33. Hisaoka T, Nakamura Y, Senba E, Morikawa Y. The forkhead transcription factors, Foxp1 and Foxp2, identify different subpopulations of projection neurons in the mouse cerebral cortex. Neuroscience. 2010;166:551-63 pubmed publisher
  34. Chen J, Chen P, Chiang Y. Molecular mechanisms of psychostimulant addiction. Chang Gung Med J. 2009;32:148-54 pubmed
    ..This review outlines the cellular pathways that have been demonstrated to participate in psychostimulant addiction, focused particularly in the nucleus accumbens. ..
  35. Chen J, Yu L, Shen H, He J, Wang X, Zheng R. What knock-out animals tell us about the effects of caffeine. J Alzheimers Dis. 2010;20 Suppl 1:S17-24 pubmed publisher
  36. Valjent E, Bertran Gonzalez J, Aubier B, Greengard P, Herve D, Girault J. Mechanisms of locomotor sensitization to drugs of abuse in a two-injection protocol. Neuropsychopharmacology. 2010;35:401-15 pubmed publisher
    ..It provides a simple and sensitive paradigm to study the mechanisms of long-term effects of drugs of abuse. ..
  37. Abdolahi A, Acosta G, Breslin F, Hemby S, Lynch W. Incubation of nicotine seeking is associated with enhanced protein kinase A-regulated signaling of dopamine- and cAMP-regulated phosphoprotein of 32 kDa in the insular cortex. Eur J Neurosci. 2010;31:733-41 pubmed publisher
  38. Qi Z, Miller G, Voit E. The internal state of medium spiny neurons varies in response to different input signals. BMC Syst Biol. 2010;4:26 pubmed publisher
  39. Molteni R, Calabrese F, Racagni G, Fumagalli F, Riva M. Antipsychotic drug actions on gene modulation and signaling mechanisms. Pharmacol Ther. 2009;124:74-85 pubmed publisher
  40. Wittköpper K, Fabritz L, Neef S, Ort K, Grefe C, Unsöld B, et al. Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging. J Clin Invest. 2010;120:617-26 pubmed publisher
    ..These data should be considered in the development of novel therapies for heart failure. ..
  41. Liu M, Choi D, Hunter R, Pandya J, Cass W, Sullivan P, et al. Trichloroethylene induces dopaminergic neurodegeneration in Fisher 344 rats. J Neurochem. 2010;112:773-83 pubmed publisher
    ..Overall, our animal model exhibits some important features of Parkinsonism, and further supports that trichloroethylene may be an environmental risk factors for Parkinson's disease. ..
  42. Yamamoto Y, Tanahashi T, Kawai T, Chikahisa S, Katsuura S, Nishida K, et al. Changes in behavior and gene expression induced by caloric restriction in C57BL/6 mice. Physiol Genomics. 2009;39:227-35 pubmed publisher
    ..Our results suggest that CR may change behavior through altered gene expression. ..
  43. Botsakis K, Pavlou O, Poulou P, Matsokis N, Angelatou F. Blockade of adenosine A2A receptors downregulates DARPP-32 but increases ERK1/2 activity in striatum of dopamine deficient "weaver" mouse. Neurochem Int. 2010;56:245-9 pubmed publisher
    ..This could be of clinical relevance since A(2A) antagonists are already used in clinical trials for ameliorating Parkinson's disease (PD) symptoms. ..
  44. Valjent E, Bertran Gonzalez J, Herve D, Fisone G, Girault J. Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice. Trends Neurosci. 2009;32:538-47 pubmed publisher
    ..Thus, BAC transgenic mice are changing the way to conceive experiments and provide an opportunity to fill the gaps between molecular and systems neurosciences. ..
  45. Puerta E, Hervias I, Barros Miñones L, Jordan J, Ricobaraza A, Cuadrado Tejedor M, et al. Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF. Neurobiol Dis. 2010;38:237-45 pubmed publisher
    ..These data encourage further evaluation of PDE5 inhibitors in transgenic mouse models of HD. ..
  46. Gu L, Waliany S, Kane S. Darpp-32 and its truncated variant t-Darpp have antagonistic effects on breast cancer cell growth and herceptin resistance. PLoS ONE. 2009;4:e6220 pubmed publisher
    ..t-Darpp and Darpp-32 appear to have antagonistic effects on Herceptin resistance. We present a unified model by which these effects might be mediated via the PKA regulatory network. ..
  47. Sarantis K, Matsokis N, Angelatou F. Synergistic interactions of dopamine D1 and glutamate NMDA receptors in rat hippocampus and prefrontal cortex: involvement of ERK1/2 signaling. Neuroscience. 2009;163:1135-45 pubmed publisher
  48. Mani S, Portillo W, Reyna A. Steroid hormone action in the brain: cross-talk between signalling pathways. J Neuroendocrinol. 2009;21:243-7 pubmed publisher
    ..The molecular mechanisms, by which a multitude of signals converge with steroid receptors to delineate a genomic level of cross-talk in brain and behaviour are discussed. ..
  49. Hsu C, Chen C, Wang C, Chiu T. Caffeine and a selective adenosine A2A receptor antagonist induce reward and sensitization behavior associated with increased phospho-Thr75-DARPP-32 in mice. Psychopharmacology (Berl). 2009;204:313-25 pubmed publisher
    ..Caffeine-induced reinforcing effect and behavioral sensitization are mediated by antagonism at adenosine A(2A) receptor. These effects are associated with phosphorylation of DARPP-32 at Thr75 in the striatum. ..
  50. Yang J, Li M, Hong L, Zhang H, Sun L, Wang W. Preparation of a novel monoclonal antibody specific to DARPP-32. Hybridoma (Larchmt). 2010;29:351-4 pubmed publisher
    ..The results showed that DARPP-32 might play an important role in carcinogenesis and multidrug resistance of gastric cancer. ..
  51. Santini E, Sgambato Faure V, Li Q, Savasta M, Dovero S, Fisone G, et al. Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia. PLoS ONE. 2010;5:e12322 pubmed publisher
    ..However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia...
  52. Elshatory Y, Gan L. The LIM-homeobox gene Islet-1 is required for the development of restricted forebrain cholinergic neurons. J Neurosci. 2008;28:3291-7 pubmed publisher
    ..Together, these results demonstrate the requirement for Isl1 in the development of restricted telencephalic cholinergic neurons and link the development of cholinergic neurons in anatomically disparate sites to Isl1 function. ..
  53. Hamel S, Bouchard A, Ferrario C, Hassan S, Aguilar Mahecha A, Buchanan M, et al. Both t-Darpp and DARPP-32 can cause resistance to trastuzumab in breast cancer cells and are frequently expressed in primary breast cancers. Breast Cancer Res Treat. 2010;120:47-57 pubmed publisher
    ..Thus, t-Darpp and DARPP-32 expression are novel prognostic and predictive biomarkers in breast cancer. ..