Thr34
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Home > Phosphorylation Site Page: > Thr34  -  DARPP-32 (mouse)

Site Information
MIRRRRPtPAMLFRV   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448047

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 3 , 5 , 32 , 38 ) , mass spectrometry ( 5 , 9 , 14 ) , modification-specific antibody ( 15 ) , mutation of modification site ( 4 , 5 , 10 , 15 , 20 , 22 , 23 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 8 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 19 , 22 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 ) , western blotting ( 2 , 3 , 4 , 5 , 8 , 10 , 12 , 13 , 15 , 16 , 17 , 19 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 39 , 40 , 41 , 42 , 44 )
Disease tissue studied:
Huntington's disease ( 41 )
Relevant cell line - cell type - tissue:
'brain, amygdala' ( 8 ) , 'brain, cerebral cortex' ( 16 , 38 ) , 'brain, hippocampus' ( 8 ) , 'brain, hypothalamus' ( 42 ) , 'brain, neostriatum' ( 26 , 30 , 33 , 40 ) , 'brain, nucleus accumbens' ( 2 , 15 ) , 'brain, striatum' ( 2 , 3 , 4 , 5 , 8 , 10 , 11 , 12 , 13 , 15 , 16 , 19 , 22 , 23 , 24 , 25 , 28 , 29 , 34 , 37 , 38 , 39 , 44 ) , 'brain, striatum' [ARPP-21 (mouse), homozygous knockout] ( 32 ) , 'brain, striatum' [DARPP-32 (mouse)] ( 27 ) , 'neuron, cerebellar granule'-brain ( 44 ) , 'neuron, cortical' ( 17 ) , 'neuron, cortical'-brain ( 41 ) , 'neuron, neostriatal'-brain ( 35 , 36 ) , 'neuron, striatal'-brain ( 5 ) , 'neuron, striatal'-brain [ARPP-21 (mouse), homozygous knockout] ( 32 ) , 293 (epithelial) ( 15 ) , brain ( 9 , 14 , 20 ) , brain [DARPP-32 (mouse), homozygous knockout] ( 31 ) , COS (fibroblast) ( 5 ) , heart ( 9 ) , lung ( 9 ) , Neuro-2a (neuron) ( 17 ) , neuron-'brain, hippocampus' ( 37 ) , neuron:synaptosome-'brain, cerebral cortex' ( 37 )

Upstream Regulation
Regulatory protein:
ADORA2A (mouse) ( 27 ) , ARPP-21 (mouse) ( 8 , 32 ) , CDK5 (mouse) ( 4 ) , CDK5R1 (mouse) ( 29 ) , DRD2 (mouse) ( 27 ) , NMDAR2A (mouse) ( 10 )
Putative in vivo kinases:
PKACA (mouse) ( 35 )
Kinases, in vitro:
PKACA (mouse) ( 43 )
Phosphatases, in vitro:
PPP2CA (mouse) ( 18 )
Treatments:
5-HT ( 38 ) , 5-HT4_receptor_agonists ( 38 ) , 5-HT5_receptor_agonists ( 38 ) , 7-NINA ( 30 ) , 8-(3-chlorostyryl) caffeine ( 35 ) , alpha-BTX ( 33 ) , AM404 ( 27 ) , caffeine ( 13 , 19 ) , cAMP_analog ( 35 , 39 ) , CGS_21680 ( 12 , 19 , 35 ) , ciclosporin ( 30 , 32 , 33 , 40 ) , clozapine ( 13 ) , CNQX ( 30 , 33 ) , cobalt ( 36 ) , cocaine ( 13 , 22 , 29 , 39 , 40 ) , colforsin ( 15 , 17 , 18 , 19 , 35 , 39 , 41 ) , CP-55940 ( 27 ) , DHbetaE ( 33 ) , DHPG ( 35 ) , dopamine ( 39 ) , estradiol ( 42 ) , eticlopride ( 24 ) , fluoxetine ( 37 ) , glutamic acid ( 30 ) , haloperidol ( 2 , 13 , 24 ) , IBMX ( 35 ) , ionomycin ( 17 ) , isoflurane ( 16 ) , ketamine ( 16 ) , levamfetamine ( 15 , 28 , 31 ) , LY367385 ( 30 , 35 ) , mecamylamine ( 33 ) , metamfetamine ( 40 ) , MK801 ( 30 , 31 , 33 , 36 ) , MPEP ( 30 , 35 ) , neurotensin ( 36 ) , nicotine ( 25 , 26 , 33 ) , nomifensine ( 39 ) , ODQ ( 12 , 30 ) , okadaic_acid ( 15 , 30 ) , papaverine ( 12 ) , PCP ( 16 ) , PD98059 ( 35 ) , progesterone ( 42 ) , propofol ( 16 ) , quinpirole ( 2 , 12 , 13 , 24 , 32 , 34 , 39 ) , raclopride ( 12 , 33 , 39 ) , RAMH ( 3 ) , rimonabant ( 27 ) , rolipram ( 12 ) , SCH_23390 ( 12 , 33 , 35 , 36 , 39 ) , seliciclib ( 43 ) , SKF38393 ( 42 ) , SKF81297 ( 12 , 13 , 15 , 32 , 34 , 35 , 39 , 41 ) , sphingosine_1-phosphate ( 11 ) , SR142948 ( 36 ) , t-ACPD ( 35 ) , TTX ( 36 ) , U0126 ( 30 , 35 ) , U73122 ( 30 ) , ZM241385 ( 12 , 35 )

Downstream Regulation
Effects of modification on DARPP-32:
activity, induced ( 20 , 23 , 42 ) , enzymatic activity, induced ( 18 ) , phosphorylation ( 15 )
Effects of modification on biological processes:
transcription, altered ( 23 )

Disease / Diagnostics Relevance
Relevant diseases:
depression ( 10 ) , Huntington's disease ( 41 )

References 

1

Carratalá-Ros C, et al. (2021) Energizing effects of bupropion on effortful behaviors in mice under positive and negative test conditions: modulation of DARPP-32 phosphorylation patterns. Psychopharmacology (Berl)
34498115   Curated Info

2

Engmann O, Giralt A, Girault JA (2016) Acute drug-induced spine changes in the nucleus accumbens are dependent on β-adducin. Neuropharmacology 110, 333-42
27480796   Curated Info

3

Rapanelli M, et al. (2016) The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons. J Biol Chem 291, 21042-21052
27510032   Curated Info

4

Plattner F, et al. (2015) The role of ventral striatal cAMP signaling in stress-induced behaviors. Nat Neurosci 18, 1094-100
26192746   Curated Info

5

Engmann O, et al. (2015) DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons. Nat Commun 6, 10099
26639316   Curated Info

6

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

7

Qin Z, et al. (2013) Isoaspartate accumulation in mouse brain is associated with altered patterns of protein phosphorylation and acetylation, some of which are highly sex-dependent. PLoS One 8, e80758
24224061   Curated Info

8

Davis MM, et al. (2012) Regulator of calmodulin signaling knockout mice display anxiety-like behavior and motivational deficits. Eur J Neurosci 35, 300-8
22250817   Curated Info

9

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
21183079   Curated Info

10

Taniguchi S, et al. (2009) Involvement of NMDAR2A tyrosine phosphorylation in depression-related behaviour. EMBO J 28, 3717-29
19834457   Curated Info

11

Heiman M, et al. (2008) A translational profiling approach for the molecular characterization of CNS cell types. Cell 135, 738-48
19013281   Curated Info

12

Nishi A, et al. (2008) Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci 28, 10460-71
18923023   Curated Info

13

Bateup HS, et al. (2008) Cell type-specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs. Nat Neurosci 11, 932-9
18622401   Curated Info

14

Zhou J (2008) CST Curation Set: 4863; Year: 2008; Biosample/Treatment: tissue, brain/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-Thr-Pro Motif Antibody (polyAB) Cat#: 3003, PTMScan(R) Phospho-Thr-Pro Motif (T*P) Immunoaffinity Beads Cat#: 1996
Curated Info

15

Stipanovich A, et al. (2008) A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature 453, 879-84
18496528   Curated Info

16

Snyder GL, Galdi S, Hendrick JP, Hemmings HC (2007) General anesthetics selectively modulate glutamatergic and dopaminergic signaling via site-specific phosphorylation in vivo. Neuropharmacology 53, 619-30
17826804   Curated Info

17

Ahn JH, et al. (2007) The B''/PR72 subunit mediates Ca2+-dependent dephosphorylation of DARPP-32 by protein phosphatase 2A. Proc Natl Acad Sci U S A 104, 9876-81
17535922   Curated Info

18

Ahn JH, et al. (2007) Protein kinase A activates protein phosphatase 2A by phosphorylation of the B56delta subunit. Proc Natl Acad Sci U S A 104, 2979-84
17301223   Curated Info

19

Sahin B, et al. (2007) Evaluation of neuronal phosphoproteins as effectors of caffeine and mediators of striatal adenosine A2A receptor signaling. Brain Res 1129, 1-14
17157277   Curated Info

20

Yan L, et al. (2006) DARPP-32 involvement in the photic pathway of the circadian system. J Neurosci 26, 9434-8
16971527   Curated Info

21

Lindskog M, et al. (2006) Transient calcium and dopamine increase PKA activity and DARPP-32 phosphorylation. PLoS Comput Biol 2, e119
16965177   Curated Info

22

Zhang Y, et al. (2006) Cocaine self-administration in mice is inversely related to phosphorylation at Thr34 (protein kinase A site) and Ser130 (kinase CK1 site) of DARPP-32. J Neurosci 26, 2645-51
16525043   Curated Info

23

Zachariou V, et al. (2006) Phosphorylation of DARPP-32 at Threonine-34 is required for cocaine action. Neuropsychopharmacology 31, 555-62
16123776   Curated Info

24

Håkansson K, et al. (2006) Regulation of phosphorylation of the GluR1 AMPA receptor by dopamine D2 receptors. J Neurochem 96, 482-8
16336634   Curated Info

25

Zhu H, et al. (2005) DARPP-32 phosphorylation opposes the behavioral effects of nicotine. Biol Psychiatry 58, 981-9
16084497   Curated Info

26

Hamada M, et al. (2005) Nicotine regulates DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) phosphorylation at multiple sites in neostriatal neurons. J Pharmacol Exp Ther 315, 872-8
16040813   Curated Info

27

Andersson M, et al. (2005) Cannabinoid action depends on phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa at the protein kinase A site in striatal projection neurons. J Neurosci 25, 8432-8
16162925   Curated Info

28

Beaulieu JM, et al. (2005) An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122, 261-73
16051150   Curated Info

29

Takahashi S, et al. (2005) Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling. Proc Natl Acad Sci U S A 102, 1737-42
15665076   Curated Info

30

Nishi A, et al. (2005) Glutamate regulation of DARPP-32 phosphorylation in neostriatal neurons involves activation of multiple signaling cascades. Proc Natl Acad Sci U S A 102, 1199-204
15657149   Curated Info

31

Valjent E, et al. (2005) Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proc Natl Acad Sci U S A 102, 491-6
15608059   Curated Info

32

Rakhilin SV, et al. (2004) A network of control mediated by regulator of calcium/calmodulin-dependent signaling. Science 306, 698-701
15499021   Curated Info

33

Hamada M, et al. (2004) Differential regulation of dopamine D1 and D2 signaling by nicotine in neostriatal neurons. J Neurochem 90, 1094-103
15312165   Curated Info

34

Lindgren N, et al. (2003) Distinct roles of dopamine D2L and D2S receptor isoforms in the regulation of protein phosphorylation at presynaptic and postsynaptic sites. Proc Natl Acad Sci U S A 100, 4305-9
12651945   Curated Info

35

Nishi A, et al. (2003) Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc Natl Acad Sci U S A 100, 1322-7
12538871   Curated Info

36

Matsuyama S, et al. (2002) Neurotensin regulates DARPP-32 thr34 phosphorylation in neostriatal neurons by activation of dopamine D1-type receptors. J Neurochem 81, 325-34
12064480   Curated Info

37

Svenningsson P, et al. (2002) Involvement of striatal and extrastriatal DARPP-32 in biochemical and behavioral effects of fluoxetine (Prozac). Proc Natl Acad Sci U S A 99, 3182-7
11880651   Curated Info

38

Svenningsson P, et al. (2002) DARPP-32 mediates serotonergic neurotransmission in the forebrain. Proc Natl Acad Sci U S A 99, 3188-93
11880652   Curated Info

39

Nishi A, et al. (2000) Amplification of dopaminergic signaling by a positive feedback loop. Proc Natl Acad Sci U S A 97, 12840-5
11050161   Curated Info

40

Snyder GL, et al. (2000) Regulation of phosphorylation of the GluR1 AMPA receptor in the neostriatum by dopamine and psychostimulants in vivo. J Neurosci 20, 4480-8
10844017   Curated Info

41

Bibb JA, et al. (2000) Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. Proc Natl Acad Sci U S A 97, 6809-14
10829080   Curated Info

42

Mani SK, et al. (2000) Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice. Science 287, 1053-6
10669419   Curated Info

43

Bibb JA, et al. (1999) Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature 402, 669-71
10604473   Curated Info

44

Snyder GL, et al. (1992) Phosphorylation of DARPP-32 and protein phosphatase inhibitor-1 in rat choroid plexus: regulation by factors other than dopamine. J Neurosci 12, 3071-83
1494946   Curated Info