Ser19

Site Information
KGFRRAVsEQDAKQA SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448542

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 21 , 22 , 23 ) , immunoprecipitation ( 18 , 20 ) , mass spectrometry ( 4 ) , microscopy-colocalization with upstream kinase ( 7 ) , mutation of modification site ( 13 ) , peptide sequencing ( 22 , 23 ) , phospho-antibody ( 1 , 2 , 3 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 14 , 16 , 17 , 18 , 19 , 20 ) , phosphoamino acid analysis ( 22 , 23 ) , phosphopeptide mapping ( 21 , 22 , 23 ) , western blotting ( 1 , 2 , 3 , 5 , 6 , 7 , 10 , 16 , 19 , 20 )
Disease tissue studied:	adrenal cancer ( 6 , 16 , 19 , 23 ) , pheochromocytoma ( 6 , 16 , 19 , 23 ) , pituitary cancer ( 19 ) , prostate cancer ( 7 )
Relevant cell line - cell type - tissue:	'brain, caudate-putamen' ( 2 , 14 ) , 'brain, hypothalamus' ( 10 , 12 ) , 'brain, nucleus accumbens' ( 14 ) , 'brain, striatum' ( 2 , 5 , 17 , 19 ) , 'brain, substantia nigra' ( 2 ) , 'brain, ventral tegmental area' ( 2 ) , 'neuron, cortical'-brain ( 11 , 18 ) , 'neuron, mesencephalic' ( 8 ) , 'neuron, substantia nigra'-brain ( 11 ) , 293 (epithelial) ( 13 ) , A126-1B2 (chromaffin) ( 16 ) , adrenal gland ( 3 , 7 ) , AtT20 (pituitary cell) ( 19 , 20 ) , brain ( 3 ) , muscle ( 1 ) , neuron-brain ( 7 ) , PC-12 (chromaffin) [TrkA (rat), transfection] ( 4 ) , PC-12 (chromaffin) ( 4 , 6 , 16 , 19 , 20 , 23 ) , PC3 (prostate cell) ( 7 )

Upstream Regulation
Regulatory protein:	GFRA1 (rat) ( 11 ) , GLT1 (rat) ( 5 )
Kinases, in vitro:	CAMK1A (human) ( 24 ) , CAMK2A (rat) ( 15 )
Putative upstream phosphatases:	PPP2CB (rat) ( 7 )
Phosphatases, in vitro:	PPP2CB (rat) ( 7 )
Treatments:	A23187 ( 23 ) , angiotensin ( 12 ) , apomorphine ( 19 ) , APV ( 18 ) , Ba(2+) ( 21 ) , bradykinin ( 21 ) , butyrolactone ( 19 ) , CHIR99021 ( 1 ) , cocaine ( 14 ) , colforsin ( 16 , 18 , 22 ) , depolarization ( 6 , 16 , 20 , 22 , 23 ) , DHPG ( 8 ) , Dihydrokainic acid ( 5 ) , EGF ( 23 ) , EGTA ( 23 ) , electrical_stimulation ( 22 ) , eticlopride ( 17 ) , GDNF ( 8 , 11 ) , genistein ( 21 ) , glutamic acid ( 8 ) , insulin ( 3 ) , lithium ( 1 ) , LPS ( 2 ) , nerve_damage ( 19 ) , nicotine ( 23 ) , NMDA ( 8 , 17 , 18 ) , NSD-1015 ( 19 ) , okadaic_acid ( 7 , 17 , 18 , 23 ) , PD98059 ( 16 ) , phorbol_ester ( 22 ) , PRL ( 10 ) , quinpirole ( 17 ) , Time ( 2 ) , veratridine ( 23 )

Downstream Regulation
Effects of modification on TH:	enzymatic activity, induced ( 12 , 18 , 20 ) , molecular association, regulation ( 13 ) , protein conformation ( 15 ) , protein stabilization ( 9 )
Induce interaction with:	14-3-3 theta (human) ( 13 )

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	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
3	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
4	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
5	Salvatore MF, Davis RW, Arnold JC, Chotibut T (2012) Transient striatal GLT-1 blockade increases EAAC1 expression, glutamate reuptake, and decreases tyrosine hydroxylase phosphorylation at ser(19). Exp Neurol 234, 428-36 22285253 Curated Info
6	Coultrap SJ, et al. (2010) CaMKII autonomy is substrate-dependent and further stimulated by Ca2+/calmodulin. J Biol Chem 285, 17930-7 20353941 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	Kobori N, Moore AN, Dash PK (2006) GDNF abates serum deprivation-induced tyrosine hydroxylase Ser19 phosphorylation and activity. Brain Res 1086, 142-51 16626642 Curated Info
9	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
10	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
11	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
12	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
13	Sachs NA, Vaillancourt RR (2004) Cyclin-dependent kinase 11p110 and casein kinase 2 (CK2) inhibit the interaction between tyrosine hydroxylase and 14-3-3. J Neurochem 88, 51-62 14675149 Curated Info
14	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
15	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
16	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
17	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
18	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
19	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
20	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
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
24	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