Thr75
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Home > Phosphorylation Site Page: > Thr75  -  DARPP-32 (mouse)

Site Information
RPNPCAYtPPSLKAV   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448048

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 2 ) , immunoprecipitation ( 4 , 6 , 28 , 31 ) , mass spectrometry ( 6 , 8 , 9 ) , mutation of modification site ( 5 , 6 , 15 , 18 , 19 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 ) , western blotting ( 3 , 4 , 5 , 6 , 10 , 12 , 13 , 14 , 15 , 16 , 23 , 24 , 25 , 26 , 30 , 31 )
Disease tissue studied:
neuroblastoma ( 25 )
Relevant cell line - cell type - tissue:
'brain, cerebral cortex' ( 13 , 28 ) , 'brain, neostriatum' ( 21 , 22 , 24 , 25 , 29 ) , 'brain, nucleus accumbens' ( 2 , 3 ) , 'brain, striatum' ( 3 , 4 , 5 , 6 , 10 , 13 , 16 , 18 , 19 , 20 , 23 , 26 , 27 , 28 , 30 , 31 ) , 'neuron, cortical' ( 14 ) , 'neuron, striatal'-brain ( 6 , 11 ) , 293 (epithelial) ( 15 ) , brain ( 8 , 9 ) , COS (fibroblast) ( 6 ) , kidney ( 9 ) , Neuro-2a (neuron) ( 14 , 25 ) , neuron ( 2 ) , neuron-'brain, hippocampus' ( 27 ) , neuron:synaptosome-'brain, cerebral cortex' ( 27 )

Upstream Regulation
Regulatory protein:
CDK5 (mouse) ( 5 ) , CDK5R1 (mouse) ( 23 ) , CK1E (mouse) ( 29 )
Putative in vivo kinases:
CDK5 (mouse) ( 12 , 23 , 25 , 29 )
Putative upstream phosphatases:
PPP2CA (mouse) ( 14 , 26 )
Phosphatases, in vitro:
PPP2CA (mouse) ( 15 )
Treatments:
5-HT ( 28 ) , 5-HT4_receptor_agonists ( 28 ) , 5-HT5_receptor_agonists ( 28 ) , allosterpaullone ( 22 ) , alpha-BTX ( 21 ) , AMPA ( 12 , 14 ) , APV ( 12 ) , BAPTA-AM ( 14 , 25 ) , butyrolactone ( 22 , 29 ) , caffeine ( 2 , 3 , 10 , 16 , 26 ) , calyculin_A ( 12 ) , cAMP_analog ( 30 ) , CGS_21680 ( 26 ) , ciclosporin ( 24 , 25 , 30 ) , CK1-7 ( 29 ) , clozapine ( 10 ) , CNQX ( 21 , 24 ) , cocaine ( 10 , 18 , 30 ) , colforsin ( 15 , 30 ) , depolarization ( 12 ) , DHbetaE ( 21 ) , DHPG ( 25 , 29 ) , dopamine ( 30 ) , EGTA ( 12 ) , ethanol ( 2 ) , fluoxetine ( 27 ) , glutamic acid ( 24 ) , haloperidol ( 3 , 10 ) , IC261 ( 29 ) , ionomycin ( 14 , 25 ) , isoflurane ( 13 ) , kainic_acid ( 12 ) , ketamine ( 13 ) , LY367385 ( 24 ) , mecamylamine ( 21 ) , MK801 ( 12 , 21 , 24 ) , Ni(2+) ( 12 ) , nicotine ( 20 , 21 ) , nimodipine ( 12 ) , NMDA ( 12 , 14 ) , nomifensine ( 30 ) , okadaic_acid ( 12 , 22 , 24 , 26 , 30 ) , phorbol_ester ( 11 ) , propofol ( 13 ) , purvalanol ( 22 ) , quinpirole ( 3 , 10 , 30 ) , raclopride ( 21 , 30 ) , RAMH ( 4 ) , SCH_23390 ( 21 , 30 ) , SCH_58261 ( 26 ) , seliciclib ( 22 , 26 , 30 , 31 ) , SKF81297 ( 10 , 30 ) , TTX ( 21 ) , U73122 ( 24 , 25 ) , ZM241385 ( 25 )

Downstream Regulation
Effects of modification on DARPP-32:
activity, induced ( 19 , 29 ) , enzymatic activity, induced ( 15 )

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

Porru S, et al. (2021) Impact of Caffeine on Ethanol Induced Stimulation and Sensitization: Changes in ERK and DARPP-32 Phosphorylation in Nucleus Accumbens. Alcohol Clin Exp Res
33471948   Curated Info

3

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

4

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

5

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

6

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

7

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

8

Goswami T, et al. (2012) Comparative phosphoproteomic analysis of neonatal and adult murine brain. Proteomics 12, 2185-9
22807455   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

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

11

Sahin B, et al. (2008) Negative regulation of cyclin-dependent kinase 5 targets by protein kinase C. Eur J Pharmacol 581, 270-5
18190909   Curated Info

12

Nguyen C, et al. (2007) Differential regulation of the Cdk5-dependent phosphorylation sites of inhibitor-1 and DARPP-32 by depolarization. J Neurochem 103, 1582-93
17868322   Curated Info

13

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

14

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

15

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

16

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

17

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

18

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

19

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

20

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

21

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

22

Futter M, et al. (2005) Phosphorylation of spinophilin by ERK and cyclin-dependent PK 5 (Cdk5). Proc Natl Acad Sci U S A 102, 3489-94
15728359   Curated Info

23

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

24

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

25

Liu F, Virshup DM, Nairn AC, Greengard P (2002) Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors. J Biol Chem 277, 45393-9
12223474   Curated Info

26

Lindskog M, et al. (2002) Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine. Nature 418, 774-8
12181566   Curated Info

27

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

28

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

29

Liu F, et al. (2001) Regulation of cyclin-dependent kinase 5 and casein kinase 1 by metabotropic glutamate receptors. Proc Natl Acad Sci U S A 98, 11062-8
11572969   Curated Info

30

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

31

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