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Gene Review

Ppp1r1b  -  protein phosphatase 1, regulatory...

Rattus norvegicus

Synonyms: DARPP-32, Darpp-32, Darpp32, Dopamine-and cAMP-regulated neuronal phosphoprotein, Protein phosphatase 1 regulatory subunit 1B
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Disease relevance of Ppp1r1b


Psychiatry related information on Ppp1r1b

  • Linear regression analysis showed that measurements of striatal DARPP-32 optical density and striatal [123I]IBZM uptake of the lesioned side were highly correlated (r2=0.83; P<0.001) whereas correlation with locomotor activity was less tight (r2=0.23; P<0.05; amphetamine-induced rotational behavior was not significantly correlated) [5].
  • DARPP-32-rich zones in grafts of lateral ganglionic eminence govern the extent of functional recovery in skilled paw reaching in an animal model of Huntington's disease [6].

High impact information on Ppp1r1b

  • One mechanism involves control of PP-1 catalytic activity by DARPP-32, a dopamine- and cAMP-regulated phosphoprotein highly enriched in neostriatum [7].
  • Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin [7].
  • The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses [8].
  • When oocytes were coinjected with rat hippocampal poly(A)+ mRNA plus complementary RNA coding for DARPP-32, NMDA responses were potentiated after stimulation of PKA [8].
  • We report here that CCK-8S abolishes cAMP-dependent phosphorylation of a dopamine- and cAMP-regulated 32-kDa phosphoprotein (DARPP-32) in striatal neurons [9].

Chemical compound and disease context of Ppp1r1b


Biological context of Ppp1r1b

  • Conversely, in morphine-sensitized rats, no apparent modifications in DARPP-32 phosphorylation pattern were observed [10].
  • Overexpressed TRE-853-82Q protein led to proteolytic release of N-terminal htt fragments, nuclear aggregation, and a striatal dysfunction as revealed by decrease of DARPP-32 staining but absence of NeuN down-regulation [11].
  • DARPP-32 first appears in the rat brain at day 14 of gestation, in the anlage of the primary olfactory cortex and the caudate nucleus [12].
  • Exposure of cultures to high concentrations of L-DOPA induced the following changes: cell death in nigral and striatal neurons, aggregation of neurofilaments and focal axonal swellings, abnormal expression of DARPP-32, and activation of astroglia and microglial cells [13].
  • These results establish an assay for in vivo studies of postsynaptic responses involving second messengers in the DA system and provide direct in vivo evidence for the hypothesis that stimulation of D1 receptors increases the phosphorylation of DARPP-32, as well as several other proteins [14].

Anatomical context of Ppp1r1b


Associations of Ppp1r1b with chemical compounds

  • One notable exception is DARPP-32 (dopamine and cAMP-regulated neuronal phosphoprotein, molecular mass, 32 kDa), a third messenger that integrates multiple signaling pathways in the brain [15].
  • The cyclin-dependent kinase Cdk5 and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa)-dependent signaling have been implicated in the regulation of dopaminergic neurotransmission after chronic cocaine treatment [16].
  • We further immunoquantified DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, mw 32,000) and phosphothreonine-DARPP-32, which can be dephosphorylated at threonine sites by CaN [19].
  • Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine [19].
  • DARPP-32 was phosphorylated on threonine-34 in these slices by sodium nitroprusside (SNP), an NO donor [18].

Regulatory relationships of Ppp1r1b


Other interactions of Ppp1r1b


Analytical, diagnostic and therapeutic context of Ppp1r1b

  • They contained striatum-like patches with neurons expressing many of the neurochemicals characteristic of striatum (ACh, ChAT, calbindin-D28KD, met-enkephalin, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000 or DARPP-32), and these patches were surrounded by graft tissue expressing few of these striatal markers [25].
  • Immunohistochemistry using DARPP-32 as striatal marker and tyrosinhydroxylase as marker for nigral neurons was performed for correlation analysis of imaging and histological parameters [26].
  • We here report the pre- and postnatal distributions of DARPP-32 in the kidney as demonstrated by immunoblotting and immunohistochemistry [27].
  • Northern blot analysis indicates that the steady-state level of DARPP-32 mRNA in striatum is also unchanged by these treatments [28].
  • The regional and cellular ontogeny of the mRNA encoding the dopamine- and cAMP-regulated phosphoprotein, DARPP-32, has been studied in rat striatum by quantitative in situ hybridization histochemistry [29].


  1. Age-related alterations in tanycytes of the mediobasal hypothalamus of the male rat. Zoli, M., Ferraguti, F., Frasoldati, A., Biagini, G., Agnati, L.F. Neurobiol. Aging (1995) [Pubmed]
  2. Lack of change in striatal DARPP-32 levels following nigrostriatal dopaminergic lesions in animals and in parkinsonian syndromes in man. Raisman-Vozari, R., Girault, J.A., Moussaoui, S., Feuerstein, C., Jenner, P., Marsden, C.D., Agid, Y. Brain Res. (1990) [Pubmed]
  3. Effect of dopamine depletion on DARPP-32 protein in ischemic rat striatum. Sun, Y.F., Tang, F.M., Ding, Y.M., Chen, Y.T., Zhang, G.Y., Jin, G.Z. Acta Pharmacol. Sin. (2001) [Pubmed]
  4. Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive response in rats. Wang, C.H., Chou, W.Y., Hung, K.S., Jawan, B., Lu, C.N., Liu, J.K., Hung, Y.P., Lee, T.H. Acta Pharmacol. Sin. (2005) [Pubmed]
  5. Evaluation of [123I]IBZM pinhole SPECT for the detection of striatal dopamine D2 receptor availability in rats. Scherfler, C., Scholz, S.W., Donnemiller, E., Decristoforo, C., Oberladstätter, M., Stefanova, N., Diederen, E., Virgolini, I., Poewe, W., Wenning, G.K. Neuroimage (2005) [Pubmed]
  6. DARPP-32-rich zones in grafts of lateral ganglionic eminence govern the extent of functional recovery in skilled paw reaching in an animal model of Huntington's disease. Nakao, N., Grasbon-Frodl, E.M., Widner, H., Brundin, P. Neuroscience (1996) [Pubmed]
  7. Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin. Yan, Z., Hsieh-Wilson, L., Feng, J., Tomizawa, K., Allen, P.B., Fienberg, A.A., Nairn, A.C., Greengard, P. Nat. Neurosci. (1999) [Pubmed]
  8. The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses. Blank, T., Nijholt, I., Teichert, U., Kügler, H., Behrsing, H., Fienberg, A., Greengard, P., Spiess, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Regulation by the neuropeptide cholecystokinin (CCK-8S) of protein phosphorylation in the neostriatum. Snyder, G.L., Fisone, G., Morino, P., Gundersen, V., Ottersen, O.P., Hökfelt, T., Greengard, P. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  10. Dopamine and cyclic AMP-regulated phosphoprotein-32 phosphorylation pattern in cocaine and morphine-sensitized rats. Scheggi, S., Rauggi, R., Gambarana, C., Tagliamonte, A., De Montis, M.G. J. Neurochem. (2004) [Pubmed]
  11. Early and reversible neuropathology induced by tetracycline-regulated lentiviral overexpression of mutant huntingtin in rat striatum. Régulier, E., Trottier, Y., Perrin, V., Aebischer, P., Déglon, N. Hum. Mol. Genet. (2003) [Pubmed]
  12. Development of a dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the prenatal rat central nervous system, and its relationship to the arrival of presumptive dopaminergic innervation. Foster, G.A., Schultzberg, M., Hökfelt, T., Goldstein, M., Hemmings, H.C., Ouimet, C.C., Walaas, S.I., Greengard, P. J. Neurosci. (1987) [Pubmed]
  13. Adeno-associated virus-mediated gene transfer of human aromatic L-amino acid decarboxylase protects mixed striatal primary cultures from L-DOPA toxicity. Doroudchi, M.M., Liauw, J., Heaton, K., Zhen, Z., Forsayeth, J.R. J. Neurochem. (2005) [Pubmed]
  14. In vivo stimulation of D1 receptors increases the phosphorylation of proteins in the striatum. Lewis, R.M., Levari, I., Ihrig, B., Zigmond, M.J. J. Neurochem. (1990) [Pubmed]
  15. DARPP-32 (dopamine and 3',5'-cyclic adenosine monophosphate-regulated neuronal phosphoprotein) is essential for the maintenance of thyroid differentiation. García-Jiménez, C., Zaballos, M.A., Santisteban, P. Mol. Endocrinol. (2005) [Pubmed]
  16. Enhanced Cdk5 activity and p35 translocation in the ventral striatum of acute and chronic methamphetamine-treated rats. Chen, P.C., Chen, J.C. Neuropsychopharmacology (2005) [Pubmed]
  17. DARPP-32-like immunoreactivity in AII amacrine cells of rat retina. Partida, G.J., Lee, S.C., Haft-Candell, L., Nichols, G.S., Ishida, A.T. J. Comp. Neurol. (2004) [Pubmed]
  18. Nitric oxide/cGMP pathway stimulates phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, in the substantia nigra. Tsou, K., Snyder, G.L., Greengard, P. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  19. Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine. Lin, X.H., Hashimoto, T., Kitamura, N., Murakami, N., Shirakawa, O., Maeda, K. Synapse (2002) [Pubmed]
  20. Phosphorylation of DARPP-32 is regulated by GABA in rat striatum and substantia nigra. Snyder, G.L., Fisone, G., Greengard, P. J. Neurochem. (1994) [Pubmed]
  21. Neurotransmitter-related gene expression in intrastriatal striatal transplants--I. Phenotypical characterization of striatal and non-striatal graft regions. Campbell, K., Wictorin, K., Björklund, A. Neuroscience (1995) [Pubmed]
  22. Early specification of striatal projection neurons and interneuronal subtypes in the lateral and medial ganglionic eminence. Olsson, M., Björklund, A., Campbell, K. Neuroscience (1998) [Pubmed]
  23. Reversal of behavioural abnormalities by fetal allografts in a novel rat model of striatonigral degeneration. Wenning, G.K., Granata, R., Laboyrie, P.M., Quinn, N.P., Jenner, P., Marsden, C.D. Mov. Disord. (1996) [Pubmed]
  24. The mesolimbic dopaminergic response to novel palatable food consumption increases dopamine-D1 receptor-mediated signalling with complex modifications of the DARPP-32 phosphorylation pattern. Rauggi, R., Scheggi, S., Cassanelli, A., De Montis, M.G., Tagliamonte, A., Gambarana, C. J. Neurochem. (2005) [Pubmed]
  25. Influence of mesostriatal afferents on the development and transmitter regulation of intrastriatal grafts derived from embryonic striatal primordia. Liu, F.C., Dunnett, S.B., Graybiel, A.M. J. Neurosci. (1992) [Pubmed]
  26. In vivo magnetic resonance imaging of embryonic neural grafts in a rat model of striatonigral degeneration (multiple system atrophy). Schocke, M.F., Waldner, R., Puschban, Z., Kolbitsch, C., Seppi, K., Scherfler, C., Kremser, C., Zschiegner, F., Felber, S., Poewe, W., Wenning, G.K. Neuroimage (2000) [Pubmed]
  27. Distribution of dopamine- and cAMP-dependent phosphoprotein (DARPP-32) in the developing and mature kidney. Fryckstedt, J., Aperia, A., Snyder, G., Meister, B. Kidney Int. (1993) [Pubmed]
  28. Chronic treatment of rats with SCH-23390 or raclopride does not affect the concentrations of DARPP-32 or its mRNA in dopamine-innervated brain regions. Grebb, J.A., Girault, J.A., Ehrlich, M., Greengard, P. J. Neurochem. (1990) [Pubmed]
  29. Developmental regulation of phosphoprotein gene expression in the caudate-putamen of rat: an in situ hybridization study. Gustafson, E.L., Ehrlich, M.E., Trivedi, P., Greengard, P. Neuroscience (1992) [Pubmed]
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