Ser31

Site Information
KQAEAVtsPRFIGRR SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448544

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 21 , 22 , 23 ) , immunoprecipitation ( 2 ) , mass spectrometry ( 2 , 5 ) , peptide sequencing ( 22 , 23 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 6 , 7 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 ) , phosphoamino acid analysis ( 22 , 23 ) , phosphopeptide mapping ( 21 , 22 , 23 ) , western blotting ( 1 , 2 , 3 , 4 , 6 , 7 , 11 , 13 , 18 , 20 )
Disease tissue studied:	adrenal cancer ( 18 , 20 , 23 ) , pheochromocytoma ( 18 , 20 , 23 ) , pituitary cancer ( 20 ) , prostate cancer ( 7 )
Relevant cell line - cell type - tissue:	'brain, caudate-putamen' ( 3 , 17 ) , 'brain, hypothalamus' ( 11 , 15 ) , 'brain, nucleus accumbens' ( 17 ) , 'brain, striatum' ( 2 , 3 , 13 , 19 , 20 ) , 'brain, substantia nigra' ( 3 ) , 'brain, ventral tegmental area' ( 3 ) , 'neuron, cortical'-brain ( 14 ) , 'neuron, substantia nigra'-brain ( 6 , 14 ) , A126-1B2 (chromaffin) ( 18 ) , adrenal gland ( 4 , 7 ) , AtT20 (pituitary cell) ( 20 ) , brain ( 4 ) , muscle ( 1 ) , N27 (neuron) ( 6 ) , PC-12 (chromaffin) [TrkA (rat), transfection] ( 5 ) , PC-12 (chromaffin) ( 5 , 6 , 12 , 18 , 20 , 23 ) , PC3 (prostate cell) ( 7 )

Upstream Regulation
Regulatory protein:	GFRA1 (rat) ( 14 )
Putative in vivo kinases:	CDK5 (rat) ( 12 ) , ERK1 (rat) ( 21 ) , ERK2 (rat) ( 21 ) , MEK1 (rat) ( 12 ) , PKCB (rat) ( 22 )
Kinases, in vitro:	ERK1 (mouse) ( 21 ) , ERK1 (rat) ( 21 ) , ERK2 (human) ( 8 , 9 ) , ERK2 (mouse) ( 21 ) , ERK2 (rat) ( 16 , 21 )
Putative upstream phosphatases:	PPP2CB (rat) ( 7 )
Phosphatases, in vitro:	PPP2CB (rat) ( 7 )
Treatments:	A23187 ( 23 ) , angiotensin ( 15 ) , apomorphine ( 20 ) , ATP ( 21 ) , Ba(2+) ( 21 ) , bradykinin ( 21 ) , butyrolactone ( 20 ) , CHIR99021 ( 1 ) , cocaine ( 13 , 17 ) , colforsin ( 18 , 22 ) , depolarization ( 18 , 22 ) , EGF ( 23 ) , electrical_stimulation ( 22 ) , GDNF ( 14 ) , genistein ( 21 ) , haloperidol ( 20 ) , insulin ( 4 ) , lithium ( 1 ) , LPS ( 3 ) , muscarine ( 21 ) , nerve_damage ( 20 ) , NGF ( 18 , 21 , 23 ) , NSD-1015 ( 20 ) , okadaic_acid ( 2 , 7 , 19 , 20 , 23 ) , olomoucine ( 12 ) , PD98059 ( 2 , 12 , 18 ) , PDGF ( 5 ) , phorbol_ester ( 21 , 22 , 23 ) , PRL ( 11 ) , quinpirole ( 19 ) , rottlerin ( 6 ) , seliciclib ( 12 ) , t-Bu2BHQ ( 21 ) , thapsigargin ( 21 ) , Time ( 3 ) , U0126 ( 12 )

Downstream Regulation
Effects of modification on TH:	enzymatic activity, induced ( 15 , 17 , 21 ) , protein stabilization ( 10 )

References
1	Hamdon S, et al. (2023) CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum. Neuropharmacology 242, 109759 37844866 Curated Info
2	González-Sepúlveda M, et al. (2022) Spontaneous changes in brain striatal dopamine synthesis and storage dynamics ex vivo reveal end-product feedback-inhibition of tyrosine hydroxylase. Neuropharmacology 212, 109058 35429504 Curated Info
3	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
4	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
5	Biarc J, Chalkley RJ, Burlingame AL, Bradshaw RA (2012) The induction of serine/threonine protein phosphorylations by a PDGFR/TrkA chimera in stably transfected PC12 cells. Mol Cell Proteomics 11, 15-30 22027198 Curated Info
6	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
7	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
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	Moy LY, Tsai LH (2004) Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and regulates its stability. J Biol Chem 279, 54487-93 15471880 Curated Info
13	Kansy JW, et al. (2004) Identification of tyrosine hydroxylase as a physiological substrate for Cdk5. J Neurochem 91, 374-84 15447670 Curated Info
14	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
15	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
16	Royo M, Daubner SC, Fitzpatrick PF (2004) Specificity of the MAP kinase ERK2 for phosphorylation of tyrosine hydroxylase. Arch Biochem Biophys 423, 247-52 15001389 Curated Info
17	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
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	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
21	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
22	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
23	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