Ser40
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Home > Phosphorylation Site Page: > Ser40  -  TH (rat)

Site Information
RFIGRRQsLIEDARK   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448545

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 23 , 24 , 25 ) , immunoprecipitation ( 20 , 22 ) , peptide sequencing ( 24 , 25 ) , phospho-antibody ( 2 , 4 , 5 , 6 , 7 , 11 , 12 , 13 , 14 , 16 , 18 , 19 , 20 , 21 , 22 ) , phosphoamino acid analysis ( 24 , 25 ) , phosphopeptide mapping ( 23 , 24 , 25 ) , western blotting ( 2 , 4 , 5 , 6 , 11 , 18 , 21 , 22 )
Disease tissue studied:
adrenal cancer ( 18 , 21 , 25 ) , pheochromocytoma ( 18 , 21 , 25 ) , pituitary cancer ( 21 ) , prostate cancer ( 5 )
Relevant cell line - cell type - tissue:
'brain, caudate-putamen' ( 6 , 16 ) , 'brain, hypothalamus' ( 11 , 13 ) , 'brain, nucleus accumbens' ( 6 , 16 ) , 'brain, striatum' ( 19 , 21 ) , 'neuron, cortical'-brain ( 12 , 20 ) , 'neuron, substantia nigra'-brain ( 4 , 12 ) , 'neuron, ventral tegmental'-brain ( 7 ) , A126-1B2 (chromaffin) ( 18 ) , adrenal gland ( 2 , 5 ) , AtT20 (pituitary cell) ( 21 , 22 ) , brain ( 2 ) , N27 (neuron) ( 4 ) , PC-12 (chromaffin) ( 4 , 14 , 18 , 21 , 22 , 25 ) , PC3 (prostate cell) ( 5 )

Upstream Regulation
Regulatory protein:
GFRA1 (rat) ( 12 )
Putative in vivo kinases:
PKACA (rat) ( 18 , 24 )
Kinases, in vitro:
CAMK1A (human) ( 26 ) , CAMK2A (rat) ( 17 ) , PKACA (human) ( 8 , 9 , 26 ) , PKACA (rat) ( 14 , 17 ) , PKCA (human) ( 26 )
Putative upstream phosphatases:
PPP2CA (mouse) ( 4 ) , PPP2CB (rat) ( 5 )
Phosphatases, in vitro:
PPP2CA (rat) ( 15 ) , PPP2CB (rat) ( 5 ) , PPPM1A (human) ( 15 )
Treatments:
angiotensin ( 13 ) , apomorphine ( 21 ) , ATP ( 23 ) , bradykinin ( 23 ) , butyrolactone ( 21 ) , caffeine ( 23 ) , cAMP_analog ( 19 , 20 , 23 , 25 ) , cocaine ( 16 ) , colforsin ( 18 , 19 , 20 , 24 , 25 ) , depolarization ( 18 , 22 , 24 ) , EGF ( 25 ) , electrical_stimulation ( 24 ) , eticlopride ( 19 ) , food deprivation ( 6 ) , GDNF ( 12 ) , genistein ( 23 ) , hypoxia ( 14 ) , insulin ( 2 ) , KN-62 ( 14 ) , leptin ( 7 ) , levamfetamine ( 6 ) , muscarine ( 23 ) , nerve_damage ( 21 ) , neurotensin ( 25 ) , NGF ( 23 , 25 ) , NMDA ( 20 ) , NSD-1015 ( 21 ) , okadaic_acid ( 4 , 5 , 19 , 20 , 25 ) , PD98059 ( 14 , 18 ) , phorbol_ester ( 24 , 25 ) , PKI ( 14 ) , PRL ( 11 ) , quinpirole ( 19 ) , Ro-20-1724 ( 19 ) , rottlerin ( 4 ) , secretin human ( 25 ) , somatostatin ( 25 ) , substance_P ( 25 ) , t-Bu2BHQ ( 23 ) , thapsigargin ( 23 ) , Theophylline ( 23 ) , VIP ( 25 )

Downstream Regulation
Effects of modification on TH:
enzymatic activity, induced ( 4 , 13 , 14 , 16 , 20 , 22 , 23 ) , molecular association, regulation ( 10 ) , protein conformation ( 3 , 17 ) , protein stabilization ( 10 )

References 

1

Ong LK, et al. (2021) Peripheral inflammation induces long-term changes in tyrosine hydroxylase activation in the substantia nigra. Neurochem Int 146, 105022
33746005   Curated Info

2

Senthilkumaran M, Johnson ME, Bobrovskaya L (2016) The Effects of Insulin-Induced Hypoglycaemia on Tyrosine Hydroxylase Phosphorylation in Rat Brain and Adrenal Gland. Neurochem Res 41, 1612-24
26935743   Curated Info

3

Wang S, et al. (2011) Fluorescence spectroscopy as a probe of the effect of phosphorylation at serine 40 of tyrosine hydroxylase on the conformation of its regulatory domain. Biochemistry 50, 2364-70
21302933   Curated Info

4

Zhang D, et al. (2007) Protein kinase C delta negatively regulates tyrosine hydroxylase activity and dopamine synthesis by enhancing protein phosphatase-2A activity in dopaminergic neurons. J Neurosci 27, 5349-62
17507557   Curated Info

5

Saraf A, Virshup DM, Strack S (2007) Differential expression of the B'beta regulatory subunit of protein phosphatase 2A modulates tyrosine hydroxylase phosphorylation and catecholamine synthesis. J Biol Chem 282, 573-80
17085438   Curated Info

6

Pan Y, et al. (2006) Synthesis, protein levels, activity, and phosphorylation state of tyrosine hydroxylase in mesoaccumbens and nigrostriatal dopamine pathways of chronically food-restricted rats. Brain Res 1122, 135-42
17010321   Curated Info

7

Hommel JD, et al. (2006) Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51, 801-10
16982424   Curated Info

8

Lehmann IT, et al. (2006) Differential regulation of the human tyrosine hydroxylase isoforms via hierarchical phosphorylation. J Biol Chem 281, 17644-51
16644734   Curated Info

9

Royo M, Colette Daubner S (2006) Kinetics of regulatory serine variants of tyrosine hydroxylase with cyclic AMP-dependent protein kinase and extracellular signal-regulated protein kinase 2. Biochim Biophys Acta 1764, 786-92
16503426   Curated Info

10

Royo M, Fitzpatrick PF, Daubner SC (2005) Mutation of regulatory serines of rat tyrosine hydroxylase to glutamate: effects on enzyme stability and activity. Arch Biochem Biophys 434, 266-74
15639226   Curated Info

11

Ma FY, Grattan DR, Goffin V, Bunn SJ (2005) Prolactin-regulated tyrosine hydroxylase activity and messenger ribonucleic acid expression in mediobasal hypothalamic cultures: the differential role of specific protein kinases. Endocrinology 146, 93-102
15388649   Curated Info

12

Salvatore MF, et al. (2004) Striatal GDNF administration increases tyrosine hydroxylase phosphorylation in the rat striatum and substantia nigra. J Neurochem 90, 245-54
15198683   Curated Info

13

Ma FY, et al. (2004) Angiotensin II regulates tyrosine hydroxylase activity and mRNA expression in rat mediobasal hypothalamic cultures: the role of specific protein kinases. J Neurochem 90, 431-41
15228599   Curated Info

14

Kumar GK, et al. (2003) Activation of tyrosine hydroxylase by intermittent hypoxia: involvement of serine phosphorylation. J Appl Physiol 95, 536-44
12692140   Curated Info

15

Bevilaqua LR, et al. (2003) Role of protein phosphatase 2C from bovine adrenal chromaffin cells in the dephosphorylation of phospho-serine 40 tyrosine hydroxylase. J Neurochem 85, 1368-73
12787056   Curated Info

16

Jedynak JP, Ali SF, Haycock JW, Hope BT (2002) Acute administration of cocaine regulates the phosphorylation of serine-19, -31 and -40 in tyrosine hydroxylase. J Neurochem 82, 382-8
12124439   Curated Info

17

Bevilaqua LR, et al. (2001) Phosphorylation of Ser(19) alters the conformation of tyrosine hydroxylase to increase the rate of phosphorylation of Ser(40). J Biol Chem 276, 40411-6
11502746   Curated Info

18

Salvatore MF, Waymire JC, Haycock JW (2001) Depolarization-stimulated catecholamine biosynthesis: involvement of protein kinases and tyrosine hydroxylase phosphorylation sites in situ. J Neurochem 79, 349-60
11677263   Curated Info

19

Lindgren N, et al. (2001) Dopamine D(2) receptors regulate tyrosine hydroxylase activity and phosphorylation at Ser40 in rat striatum. Eur J Neurosci 13, 773-80
11207812   Curated Info

20

Lindgren N, et al. (2000) Regulation of tyrosine hydroxylase activity and phosphorylation at Ser(19) and Ser(40) via activation of glutamate NMDA receptors in rat striatum. J Neurochem 74, 2470-7
10820208   Curated Info

21

Lew JY, et al. (1999) Increased site-specific phosphorylation of tyrosine hydroxylase accompanies stimulation of enzymatic activity induced by cessation of dopamine neuronal activity. Mol Pharmacol 55, 202-9
9927609   Curated Info

22

Haycock JW, et al. (1998) Role of serine-19 phosphorylation in regulating tyrosine hydroxylase studied with site- and phosphospecific antibodies and site-directed mutagenesis. J Neurochem 71, 1670-5
9751201   Curated Info

23

Haycock JW, Ahn NG, Cobb MH, Krebs EG (1992) ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ. Proc Natl Acad Sci U S A 89, 2365-9
1347949   Curated Info

24

Haycock JW, Haycock DA (1991) Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. Multiple-site phosphorylation in vivo and in synaptosomes. J Biol Chem 266, 5650-7
1672315   Curated Info

25

Haycock JW (1990) Phosphorylation of tyrosine hydroxylase in situ at serine 8, 19, 31, and 40. J Biol Chem 265, 11682-91
1973163   Curated Info

26

Campbell DG, Hardie DG, Vulliet PR (1986) Identification of four phosphorylation sites in the N-terminal region of tyrosine hydroxylase. J Biol Chem 261, 10489-92
2874140   Curated Info