• In the densely dopamine- and glutamate-innervated rat caudate-putamen, DARPP32 is expressed in medium-sized spiny neurons that also express dopamine D1 receptors. (wikipedia.org)
  • Examination of the mechanism by which NMDA modulates the phosphorylation of protein phosphatase inhibitor-1 at Ser6 and Ser67 and dopamine- and cAMP-regulated phosphoprotein M r 32 000 at Thr75 revealed that generalized depolarization, rather than specific activation of NMDA receptors, was sufficient to induce decreases in these Cdk5 sites. (elsevierpure.com)
  • We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15) is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. (frontiersin.org)
  • A family of receptors (RECEPTORS, DOPAMINE) mediate its action. (lookformedical.com)
  • A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. (lookformedical.com)
  • Chen X, Jia B, Araki Y , Liu B , Ye F, Huganir R , Zhang M. Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation. (neurotree.org)
  • Because the neurobiological substrate of cariprazine has remained elusive, we took advantage of PharmacoSTORM to provide in vivo evidence that cariprazine predominantly binds to D 3 dopamine receptors on Islands of Calleja granule cell axons but avoids dopaminergic terminals. (nature.com)
  • Protein phosphatase 1 regulatory subunit 1B (PPP1R1B), also known as dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32), is a protein that in humans is encoded by the PPP1R1B gene. (wikipedia.org)
  • Also, neuronal calcium sensor-1 was suggested to modulate the expression of DARPP-32. (wikipedia.org)
  • A subfamily of MARVEL domain-containing proteins that are found in SYNAPTIC VESICLES, where they may play a role in modulating neuronal signaling. (ouhsc.edu)
  • Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5), which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) at Thr75 in the striatum. (frontiersin.org)
  • Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571), a selective c-Abl inhibitor. (frontiersin.org)
  • Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum. (frontiersin.org)
  • In the striatum, Cdk5 plays a regulatory role in the dopamine and glutamate transmissions that are integrated by DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) ( Greengard, 2001 ). (frontiersin.org)
  • Glutamate inputs activate Cdk5, which inhibits postsynaptic dopamine D1 receptor (D1R)-mediated signaling by phosphorylating DARPP-32 at Thr75 (Thr75-DARPP-32) in the striatum, since DARPP-32 with Thr75 phosphorylation (DARPP-32-pThr75) functions as an inhibitor of cAMP-dependent protein kinase A (PKA). (frontiersin.org)
  • however, it is not fully understood how Cdk5 interacts with dopamine signaling in the striatum. (frontiersin.org)
  • One of the regulatory mechanisms that modulate the Cdk5 kinase activity is phosphorylation of conserved residues ( Dhavan and Tsai, 2001 ). (frontiersin.org)
  • This strategic localization of Cdk5-pTyr15 suggests a possible role of the c-Abl/Cdk5 signaling in modulation of postsynaptic dopamine and glutamate transmissions in the striatum. (frontiersin.org)
  • Here, we show that in the mouse striatum, dopamine receptor stimulation negatively regulates phosphorylation of Tyr15-Cdk5 most likely through a D2R-mediated mechanism. (frontiersin.org)
  • attenuates abnormally increased striatal phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32, as does L-3,4-dihydroxyphenylalanine (L-dopa). (frontiersin.org)
  • These findings have important implications for understanding the mechanisms by which the Cdk5/DAPP-32-Thr75 signaling regulates the striatal functions. (frontiersin.org)
  • A considerable proportion of the psychomotor effects of cannabinoids can be accounted for by a signaling cascade in striatal projection neurons involving PKA-dependent phosphorylation of DARPP-32, achieved via modulation of dopamine D2 and adenosine A2A transmission. (wikipedia.org)
  • DARPP-32 (dopamine- and cAMP-regulated phosphorprotein, Mr = 32,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) is an inhibitor of protein phosphatase-1 and is enriched in dopaminoceptive neurons possessing the D1 dopamine receptor. (cornell.edu)
  • this is disputed by more recent research that claims cAMP signaling induces dephosphorylation of DARPP32) phosphorylated DARPP32 is a potent protein phosphatase-1 (PPP1CA) inhibitor. (wikipedia.org)
  • Purified bovine DARPP-32 was phosphorylated in vitro by casein kinase II to a stoichiometry greater than 2 mol of phosphate/mol of protein whereas two structurally and functionally related proteins, protein phosphatase inhibitor-1 and G-substrate, were poor substrates for this enzyme. (cornell.edu)
  • Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. (cornell.edu)
  • PP2A and PP1, but not Cn, are inhibited by the exogenously administered phosphatase inhibitors okadaic acid, microcystin, and calyculin, as well as the endogenous inhibitors inhibitor-1 and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa). (pancreapedia.org)
  • One well studied target for the actions of dopamine is DARPP32. (wikipedia.org)
  • The function of DARPP32 seems to be regulated by receptor stimulation. (wikipedia.org)
  • Both dopaminergic and glutamatergic (NMDA) receptor stimulation regulate the extent of DARPP32 phosphorylation, but in opposite directions. (wikipedia.org)
  • Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. (frontiersin.org)
  • In addition, various pathways and neurotransmitter systems have been found to be related to the psychoactive and addictive properties of nicotine, such as the mesocorticolimbic dopamine system [ 14 - 16 ], the serotonin system, the glutamate system, and the GABA system [ 17 - 19 ]. (hindawi.com)
  • DARPP-32 is critical for dopamine dependent striatal synaptic plasticity, possibly by serving as a dopamine-dependent gating mechanism for calcium/CaMKII signaling. (wikipedia.org)
  • It has been predicted that DARPP-32, in conjunction with ARPP-21, could also be involved in setting-up of eligibility trace-like temporal window for striatal postsynaptic signaling. (wikipedia.org)
  • Remarkably, the molecular programs regulating striatal pathway development remain poorly characterized. (jneurosci.org)
  • There are two protein products encoded by PPP1R1B: DARPP-32 and t-Darpp. (wikipedia.org)
  • In vitro, DARPP-32 phosphorylated by casein kinase II was dephosphorylated by protein phosphatases-1 and -2A. (cornell.edu)
  • However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase with a 2.2-fold increase in the Vmax and a 1.4-fold increase in the apparent Km. (cornell.edu)
  • NMDA-induced decreases in the phosphorylation of Thr75 of dopamine- and cAMP-regulated phosphoprotein M r 32 000 required protein phosphatase 1/2A activity and extracellular Ca 2+ . (elsevierpure.com)
  • 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. (lookformedical.com)
  • Further, emerging evidence suggests that nicotine can also regulate the expression of genes/proteins involved in various functions such as ERK1/2, CREB, and c-FOS [ 20 - 22 ], as well as the expression state of multiple biochemical pathways, for example, mitogen-activated protein kinase (MAPK), phosphatidylinositol phosphatase signaling, growth factor signaling, and ubiquitin-proteasome pathways [ 23 - 25 ]. (hindawi.com)
  • It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION. (ucdenver.edu)
  • Additionally, extracts of YXT and several of its constituent herbs significantly stimulated the phosphorylation of extracellular signal-regulated kinases and cAMP-responsive element binding protein, two molecular targets involved in learning and memory, as well as in the regulation of neurogenesis. (biomedcentral.com)
  • ICA69 regulates activity-dependent synaptic strengthening and learning and memory. (neurotree.org)
  • In slices of rat caudate-putamen prelabeled with [32P]phosphate, DARPP-32 was phosphorylated on seryl residues under basal conditions. (cornell.edu)
  • In the case of rat DARPP-32, the identification of these phosphorylation sites was confirmed by manual Edman degradation. (cornell.edu)
  • Dyskinesia is also accompanied by augmented activity of the extra cellular S63845 mouse signal-regulated kinases (ERK) and the mammalian target of rapamycin complex 1 (mTORC1), which are involved in the control of transcriptional and translational efficiency. (proteasomesignal.com)
  • The-174 G/C IL-6 gene promoter region single nucleotide polymorphism (SNP) may influence or modulate gene function and/or transcriptional efficiency. (proteasomesignal.com)
  • CnB, the regulatory subunit, contains 4 Ca 2+ -binding EF hand motifs that regulate (through a conformational change) the catalytic function of Cn. (pancreapedia.org)
  • This gene is also known as DARPP-32, highlighting its role as a dopamine- and cyclic AMP-regulated phosphoprotein. (wikipedia.org)
  • As the underlying mechanism of action of YXT has not been elucidated, we examined the effects of YXT and its major herbal components in regulating gene transcription and molecular targets related to Alzheimer's disease (AD). (biomedcentral.com)
  • t-Darpp is a truncated version of DARPP-32 as it is missing the first 36 amino acids at the N-terminus. (wikipedia.org)
  • These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. (lookformedical.com)
  • For instance, LID is reduced in mice deficient for DARPP-32, or following inhibition of PKA. (proteasomesignal.com)
  • This alteration is suggested to be related to the pathology, since antipsychotics do not regulate the expression of DARPP-32. (wikipedia.org)
  • Brain-derived neurotrophic factor regulates the expression of DARPP-32. (wikipedia.org)
  • DARPP-32 levels are decreased in the dorsolateral prefrontal cortex and lymphocytes of both schizophrenia and bipolar disorder patients. (wikipedia.org)