Abstract
Pyridoxal 5′-phosphate (PLP)-dependent enzymes catalyze a wide range of reactions of amino acids and amines, with the exception of glycogen phosphorylase which exhibits peculiar both substrate preference and chemical mechanism. They represent about 4% of the gene products in eukaryotic cells. Although structure–function investigations regarding these enzymes are copious, their regulation by post-translational modifications is largely unknown. Protein phosphorylation is the most common post-translational modification fundamental in mediating diverse cellular functions. This review aims at summarizing the current knowledge on regulation of PLP enzymes by phosphorylation. Starting from the paradigmatic PLP-dependent glycogen phosphorylase, the first phosphoprotein discovered, we collect data in literature regarding functional phosphorylation events of eleven PLP enzymes belonging to different fold types and discuss the impact of the modification in affecting their activity and localization as well as the implications on the pathogenesis of diseases in which many of these enzymes are involved. The pivotal question is to correlate the structural consequences of phosphorylation among PLP enzymes of different folds with the functional modifications exerted in terms of activity or conformational changes or others. Although the literature shows that the phosphorylation of PLP enzymes plays important roles in mediating diverse cellular functions, our recapitulation of clue findings in the field makes clear that there is still much to be learnt. Besides mass spectrometry-based proteomic analyses, further biochemical and structural studies on purified native proteins are imperative to fully understand and predict how phosphorylation regulates PLP enzymes and to find the relationship between addition of a phosphate moiety and physiological response.
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Abbreviations
- PLP:
-
Pyridoxal 5′-phosphate
- PTM:
-
Post-translational modification
- TAT:
-
Tyrosine aminotransferase
- GABA:
-
γ-Aminobutyric acid
- GABA-T:
-
γ-Aminobutyric acid transaminase
- SPT:
-
Serine palmitoyl transferase
- GAD:
-
Glutamate decarboxylase
- DDC:
-
DOPA decarboxylase
- AADC :
-
Aromatic amino acid decarboxylase
- HDC:
-
Histidine decarboxylase
- CSAD:
-
Cysteine sulfinic acid decarboxylase
- SR:
-
Serine racemase
- CBS:
-
Cystathionine β-synthase
- ODC:
-
Ornithine decarboxylase
- PD:
-
Parkinson’s disease
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- PKG:
-
Protein kinase G
- CaMKII:
-
Calcium–calmodulin dependent protein kinase II
- LBC1:
-
Long-chain base 1
- LBC2:
-
Long-chain base 2
- HSAN1:
-
Autonomic neuropathy type 1
- NMDA:
-
N-methyl-d-aspartate
References
Arias C, Valero H, Tapia R (1992) Inhibition of brain glutamate decarboxylase activity is related to febrile seizures in rat pups. J Neurochem 58(1):369–373
Astegno A, Capitani G, Dominici P (2015) Functional roles of the hexamer organization of plant glutamate decarboxylase. Biochim Biophys Acta 1854(9):1229–1237. https://doi.org/10.1016/j.bbapap.2015.01.001
Astegno A, La Verde V, Marino V, Dell’Orco D, Dominici P (2016) Biochemical and biophysical characterization of a plant calmodulin: role of the N- and C-lobes in calcium binding, conformational change, and target interaction. Biochim Biophys Acta 1864(3):297–307. https://doi.org/10.1016/j.bbapap.2015.12.003
Baekkeskov S, Landin M, Kristensen JK, Srikanta S, Bruining GJ, Mandrup-Poulsen T, de Beaufort C, Soeldner JS, Eisenbarth G, Lindgren F et al (1987) Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J Clin Invest 79(3):926–934. https://doi.org/10.1172/JCI112903
Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, De Camilli P (1990) Identification of the 64 K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347(6289):151–156. https://doi.org/10.1038/347151a0
Balan L, Foltyn VN, Zehl M, Dumin E, Dikopoltsev E, Knoh D, Ohno Y, Kihara A, Jensen ON, Radzishevsky IS, Wolosker H (2009) Feedback inactivation of d-serine synthesis by NMDA receptor-elicited translocation of serine racemase to the membrane. Proc Natl Acad Sci USA 106(18):7589–7594. https://doi.org/10.1073/pnas.0809442106
Bao J, Cheung WY, Wu JY (1995) Brain l-glutamate decarboxylase. Inhibition by phosphorylation and activation by dephosphorylation. J Biol Chem 270(12):6464–6467
Baumgart F, Rodriguez-Crespo I (2008) d-Amino acids in the brain: the biochemistry of brain serine racemase. FEBS J 275(14):3538–3545. https://doi.org/10.1111/j.1742-4658.2008.06517.x
Blum P, Jankovic J (1991) Stiff-person syndrome: an autoimmune disease. Mov Disord 6(1):12–20. https://doi.org/10.1002/mds.870060104
Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, Wagner-McPherson CB, Evans GA, Tobin AJ (1992) Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci USA 89(6):2115–2119
Capitani G, De Biase D, Aurizi C, Gut H, Bossa F, Grutter MG (2003) Crystal structure and functional analysis of Escherichia coli glutamate decarboxylase. EMBO J 22(16):4027–4037. https://doi.org/10.1093/emboj/cdg403
Carr RK, Schlichter D, Spielholz C, Wicks WD (1986) In vitro phosphorylation of 4-aminobutyrate aminotransferase by cAMP dependent protein kinase. J Cycl Nucleotide Protein Phosphor Res 11(1):11–23
Chou CC, Modi JP, Wang CY, Hsu PC, Lee YH, Huang KF, Wang AH, Nan C, Huang X, Prentice H, Wei J, Wu JY (2017) Activation of brain l-glutamate decarboxylase 65 isoform (GAD65) by phosphorylation at threonine 95 (T95). Mol Neurobiol 54(2):866–873. https://doi.org/10.1007/s12035-015-9633-0
Cohen P (2000) The regulation of protein function by multisite phosphorylation—a 25 year update. Trends Biochem Sci 25(12):596–601
Cohen P (2002) The origins of protein phosphorylation. Nat Cell Biol 4(5):E127–E130. https://doi.org/10.1038/ncb0502-e127
di Villa d’Emmanuele, Bianca R, Mitidieri E, Esposito D, Donnarumm E, Russo A, Fusco F, Ianaro A, Mirone V, Cirino G, Russo G, Sorrentino R (2015) Human cystathionine-β-synthase phosphorylation on serine227 modulates hydrogen sulfide production in human urothelium. PLoS ONE 10(9):e0136859. https://doi.org/10.1371/journal.pone.0136859
d’Emmanuele di Villa Bianca R, Mitidieri E, Fusco F, Russo A, Pagliara V, Tramontano T, Donnarumma E, Mirone V, Cirino G, Russo G, Sorrentino R (2016) Urothelium muscarinic activation phosphorylates CBSSer227 via cGMP/PKG pathway causing human bladder relaxation through H2S production. Sci Rep 6:31491. https://doi.org/10.1038/srep31491
Dartsch C, Chen D, Persson L (1998) Multiple forms of rat stomach histidine decarboxylase may reflect posttranslational activation of the enzyme. Regul Pept 77(1–3):33–41
Duchemin AM, Berry MD, Neff NH, Hadjiconstantinou M (2000) Phosphorylation and activation of brain aromatic L-amino acid decarboxylase by cyclic AMP-dependent protein kinase. J Neurochem 75(2):725–731
Duchemin AM, Neff NH, Hadjiconstantinou M (2010) Aromatic l-amino acid decarboxylase phosphorylation and activation by PKGIalpha in vitro. J Neurochem 114(2):542–552. https://doi.org/10.1111/j.1471-4159.2010.06784.x
Dunathan HC (1966) Conformation and reaction specificity in pyridoxal phosphate enzymes. Proc Natl Acad Sci USA 55(4):712–716
Erlander MG, Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ (1991) Two genes encode distinct glutamate decarboxylases. Neuron 7(1):91–100
Ernst D, Murphy SM, Sathiyanadan K, Wei Y, Othman A, Laura M, Liu YT, Penno A, Blake J, Donaghy M, Houlden H, Reilly MM, Hornemann T (2015) Novel HSAN1 mutation in serine palmitoyltransferase resides at a putative phosphorylation site that is involved in regulating substrate specificity. Neuromol Med 17(1):47–57. https://doi.org/10.1007/s12017-014-8339-1
Fenalti G, Law RH, Buckle AM, Langendorf C, Tuck K, Rosado CJ, Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI, Mackay IR, Rowley MJ, Whisstock JC (2007) GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop. Nat Struct Mol Biol 14(4):280–286. https://doi.org/10.1038/nsmb1228
Fleming JV, Fajardo I, Langlois MR, Sanchez-Jimenez F, Wang TC (2004) The C-terminus of rat l-histidine decarboxylase specifically inhibits enzymic activity and disrupts pyridoxal phosphate-dependent interactions with l-histidine substrate analogues. Biochem J 381(Pt 3):769–778. https://doi.org/10.1042/BJ20031553
Foltyn VN, Zehl M, Dikopoltsev E, Jensen ON, Wolosker H (2010) Phosphorylation of mouse serine racemase regulates d-serine synthesis. FEBS Lett 584(13):2937–2941. https://doi.org/10.1016/j.febslet.2010.05.022
Francis H, DeMorrow S, Venter J, Onori P, White M, Gaudio E, Francis T, Greene JF Jr, Tran S, Meininger CJ, Alpini G (2012) Inhibition of histidine decarboxylase ablates the autocrine tumorigenic effects of histamine in human cholangiocarcinoma. Gut 61(5):753–764. https://doi.org/10.1136/gutjnl-2011-300007
Grishin NV, Phillips MA, Goldsmith EJ (1995) Modeling of the spatial structure of eukaryotic ornithine decarboxylases. Protein Sci 4(7):1291–1304. https://doi.org/10.1002/pro.5560040705
Gut H, Dominici P, Pilati S, Astegno A, Petoukhov MV, Svergun DI, Grutter MG, Capitani G (2009) A common structural basis for pH- and calmodulin-mediated regulation in plant glutamate decarboxylase. J Mol Biol 392(2):334–351. https://doi.org/10.1016/j.jmb.2009.06.080
Hornykiewicz O, Lloyd KG, Davidson L (1976) The GABA system and function of the basal ganglia and Parkinson’s disease. In: Chase TN, Tower DB, Roberts E (eds) GABA in nervous system function. Raven Press, New York, pp 479–485
Hsu CC, Thomas C, Chen W, Davis KM, Foos T, Chen JL, Wu E, Floor E, Schloss JV, Wu JY (1999) Role of synaptic vesicle proton gradient and protein phosphorylation on ATP-mediated activation of membrane-associated brain glutamate decarboxylase. J Biol Chem 274(34):24366–24371
Hunter T (1995) Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80(2):225–236
Huszti Z, Magyar K (1984) Regulation of histidine decarboxylase activity in rat hypothalamus in vitro by ATP and cyclic AMP: enzyme inactivation under phosphorylating conditions. Agents Actions 14(3–4):546–549
Huszti Z, Magyar K (1985) Evidence for the role of cAMP-dependent protein kinase in the down-regulation of hypothalamic HD: reversal of cAMP-(ATP) induced inhibition of HD activity by the ‘Walsh’ inhibitor of cAMP-dependent protein kinase and by cyclic GMP. Agents Actions 16(3–4):240–243
Huszti Z, Magyar K (1987) Stimulation of hypothalamic histidine decarboxylase by calcium-calmodulin and protein kinase (cAMP-dependent) inhibitor. Agents Actions 20(3–4):233–235
Jayakrishnan B, Hoke DE, Langendorf CG, Buckle AM, Rowley MJ (2011) An analysis of the cross-reactivity of autoantibodies to GAD65 and GAD67 in diabetes. PLoS ONE 6(4):e18411. https://doi.org/10.1371/journal.pone.0018411
Jin H, Wu H, Osterhaus G, Wei J, Davis K, Sha D, Floor E, Hsu CC, Kopke RD, Wu JY (2003) Demonstration of functional coupling between gamma-aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles. Proc Natl Acad Sci USA 100(7):4293–4298. https://doi.org/10.1073/pnas.0730698100
John RA (1995) Pyridoxal phosphate-dependent enzymes. Biochim Biophys Acta 1248(2):81–96
Johnson LN (1992) Glycogen phosphorylase: control by phosphorylation and allosteric effectors. FASEB J 6(6):2274–2282
Kash SF, Johnson RS, Tecott LH, Noebels JL, Mayfield RD, Hanahan D, Baekkeskov S (1997) Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci USA 94(25):14060–14065
Kass I, Hoke DE, Costa MG, Reboul CF, Porebski BT, Cowieson NP, Leh H, Pennacchietti E, McCoey J, Kleifeld O, Borri Voltattorni C, Langley D, Roome B, Mackay IR, Christ D, Perahia D, Buckle M, Paiardini A, De Biase D, Buckle AM (2014) Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis. Proc Natl Acad Sci USA 111(25):E2524–E2529. https://doi.org/10.1073/pnas.1403182111
Kennedy L, Hodges K, Meng F, Alpini G, Francis H (2012) Histamine and histamine receptor regulation of gastrointestinal cancers. Transl Gastrointest Cancer 1(3):215–227
Klammer M, Kaminski M, Zedler A, Oppermann F, Blencke S, Marx S, Muller S, Tebbe A, Godl K, Schaab C (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteom 11(9):651–668. https://doi.org/10.1074/mcp.M111.016410
Kornev AP, Haste NM, Taylor SS, Eyck LF (2006) Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Proc Natl Acad Sci USA 103(47):17783–17788. https://doi.org/10.1073/pnas.0607656103
Langendorf CG, Tuck KL, Key TL, Fenalti G, Pike RN, Rosado CJ, Wong AS, Buckle AM, Law RH, Whisstock JC (2013) Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates. Biosci Rep 33(1):137–144. https://doi.org/10.1042/BSR20120111
Lee KL, Nickol JM (1974) Phosphorylation of tyrosine aminotransferase in vivo. J Biol Chem 249(18):6024–6026
Lu CT, Huang KY, Su MG, Lee TY, Bretana NA, Chang WC, Chen YJ, Huang HD (2013) DbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications. Nucleic Acids Res 41(database issue):D295–D305. https://doi.org/10.1093/nar/gks1229
Mann M, Jensen ON (2003) Proteomic analysis of post-translational modifications. Nat Biotechnol 21(3):255–261. https://doi.org/10.1038/nbt0303-255
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298(5600):1912–1934. https://doi.org/10.1126/science.1075762
Martin DL, Rimvall K (1993) Regulation of gamma-aminobutyric acid synthesis in the brain. J Neurochem 60(2):395–407
Mathieu C, Dupret JM, Rodrigues Lima F (2017) The structure of brain glycogen phosphorylase-from allosteric regulation mechanisms to clinical perspectives. FEBS J 284(4):546–554. https://doi.org/10.1111/febs.13937
Mertins P, Mani DR, Ruggles KV, Gillette MA, Clauser KR, Wang P, Wang X, Qiao JW, Cao S, Petralia F, Kawaler E, Mundt F, Krug K, Tu Z, Lei JT, Gatza ML, Wilkerson M, Perou CM, Yellapantula V, Huang KL, Lin C, McLellan MD, Yan P, Davies SR, Townsend RR, Skates SJ, Wang J, Zhang B, Kinsinger CR, Mesri M, Rodriguez H, Ding L, Paulovich AG, Fenyo D, Ellis MJ, Carr SA (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534(7605):55–62. https://doi.org/10.1038/nature18003
Miles EW, Kraus JP (2004) Cystathionine β-synthase: structure, function, regulation, and location of homocystinuria-causing mutations. J Biol Chem 279(29):29871–29874. https://doi.org/10.1074/jbc.R400005200
Namchuk M, Lindsay L, Turck CW, Kanaani J, Baekkeskov S (1997) Phosphorylation of serine residues 3, 6, 10, and 13 distinguishes membrane anchored from soluble glutamic acid decarboxylase 65 and is restricted to glutamic acid decarboxylase 65alpha. J Biol Chem 272(3):1548–1557
Ohtsu H (2010) Histamine synthesis and lessons learned from histidine decarboxylase deficient mice. Adv Exp Med Biol 709:21–31
Othman A, Rutti MF, Ernst D, Saely CH, Rein P, Drexel H, Porretta-Serapiglia C, Lauria G, Bianchi R, von Eckardstein A, Hornemann T (2012) Plasma deoxysphingolipids: a novel class of biomarkers for the metabolic syndrome? Diabetologia 55(2):421–431. https://doi.org/10.1007/s00125-011-2384-1
Othman A, Bianchi R, Alecu I, Wei Y, Porretta-Serapiglia C, Lombardi R, Chiorazzi A, Meregalli C, Oggioni N, Cavaletti G, Lauria G, von Eckardstein A, Hornemann T (2015) Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats. Diabetes 64(3):1035–1045. https://doi.org/10.2337/db14-1325
Paiardini A, Giardina G, Rossignoli G, Voltattorni CB, Bertoldi M (2017) New insights emerging from recent investigations on human group II pyridoxal 5′-phosphate decarboxylases. Curr Med Chem 24(3):226–244. https://doi.org/10.2174/0929867324666161123093339
Palm D, Klein HW, Schinzel R, Buehner M, Helmreich EJ (1990) The role of pyridoxal 5′-phosphate in glycogen phosphorylase catalysis. Biochemistry 29(5):1099–1107
Panula P, Nuutinen S (2013) The histaminergic network in the brain: basic organization and role in disease. Nat Rev Neurosci 14(7):472–487. https://doi.org/10.1038/nrn3526
Penno A, Reilly MM, Houlden H, Laura M, Rentsch K, Niederkofler V, Stoeckli ET, Nicholson G, Eichler F, Brown RH Jr, von Eckardstein A, Hornemann T (2010) Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. J Biol Chem 285(15):11178–11187. https://doi.org/10.1074/jbc.M109.092973
Percudani R, Peracchi A (2003) A genomic overview of pyridoxal-phosphate-dependent enzymes. EMBO Rep 4(9):850–854. https://doi.org/10.1038/sj.embor.embor914
Percudani R, Peracchi A (2009) The B6 database: a tool for the description and classification of vitamin B6-dependent enzymatic activities and of the corresponding protein families. BMC Bioinform 10:273. https://doi.org/10.1186/1471-2105-10-273
Phillips RS (2015) Chemistry and diversity of pyridoxal-5′-phosphate dependent enzymes. Biochim Biophys Acta 1854(9):1167–1174. https://doi.org/10.1016/j.bbapap.2014.12.028
Phillips RS, Scott I, Paulose R, Patel A, Barron TC (2014) The phosphate of pyridoxal-5′-phosphate is an acid/base catalyst in the mechanism of Pseudomonas fluorescens kynureninase. FEBS J 281(4):1100–1109. https://doi.org/10.1111/febs.12671
Pogson CI, Dickson AJ, Knowles RG, Salter M, Santana MA, Stanley JC, Fisher MJ (1986) Control of phenylalanine and tyrosine metabolism by phosphorylation mechanisms. Adv Enzyme Regul 25:309–327
Reddy SG, McLlheran SM, Cochran BJ, Worth LL, Bishop LA, Brown PJ, Knutson VP, Haddox MK (1996) Multisite phosphorylation of ornithine decarboxylase in transformed macrophages results in increased intracellular enzyme stability and catalytic efficiency. J Biol Chem 271(40):24945–24953
Roberts E (1975) The Nervous System. In: Tower DB (ed) The basic neurosciences, vol I. Raven Press, New York, pp 541–552
Rosenberg-Hasson Y, Strumpf D, Kahana C (1991) Mouse ornithine decarboxylase is phosphorylated by casein kinase-II at a predominant single location (serine 303). Eur J Biochem 197(2):419–424
Savany A, Cronenberger L (1982) Isolation and properties of multiple forms of histidine decarboxylase from rat gastric mucosa. Biochem J 205(2):405–412
Savany A, Cronenberger L (1988) Histidine decarboxylase from rat gastric mucosa: heterogeneity and enzyme forms modification. Biochem Int 16(3):559–570
Savany A, Cronenberger L (1989) Inactivation of rat gastric mucosal histidine decarboxylase by phosphatase. Biochem Int 19(2):429–438
Savany A, Cronenberger L (1990) Relationship between the multiple forms of rat gastric histidine decarboxylase: effects of conditions favouring phosphorylation and dephosphorylation. Biochem Int 20(2):363–374
Schmid E, Schmid W, Jantzen M, Mayer D, Jastorff B, Schutz G (1987) Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes. Eur J Biochem 165(3):499–506
Schneider G, Kack H, Lindqvist Y (2000) The manifold of vitamin B6 dependent enzymes. Structure 8(1):R1–R6
Seo J, Lee KJ (2004) Post-translational modifications and their biological functions: proteomic analysis and systematic approaches. J Biochem Mol Biol 37(1):35–44
Sherman AD, Davidson AT, Baruah S, Hegwood TS, Waziri R (1991) Evidence of glutamatergic deficiency in schizophrenia. Neurosci Lett 121(1–2):77–80
Singh V, Ram M, Kumar R, Prasad R, Roy BK, Singh KK (2017) Phosphorylation: implications in Cancer. Protein J 36(1):1–6. https://doi.org/10.1007/s10930-017-9696-z
Soghomonian JJ, Laprade N (1997) Glutamate decarboxylase (GAD67 and GAD65) gene expression is increased in a subpopulation of neurons in the putamen of Parkinsonian monkeys. Synapse 27(2):122–132. https://doi.org/10.1002/(SICI)1098-2396(199710)27:2<122:AID-SYN3>3.0.CO;2-G
Spielholz C, Carr K, Schlichter D, Wicks WD (1984) In vitro phosphorylation of tyrosine and 4-aminobutyrate aminotransferases by cAMP dependent protein kinase. Prog Clin Biol Res 144B:57–66
Sprang SR, Acharya KR, Goldsmith EJ, Stuart DI, Varvill K, Fletterick RJ, Madsen NB, Johnson LN (1988) Structural changes in glycogen phosphorylase induced by phosphorylation. Nature 336(6196):215–221. https://doi.org/10.1038/336215a0
Stirtan WG, Withers SG (1996) Phosphonate and alpha-fluorophosphonate analogue probes of the ionization state of pyridoxal 5′-phosphate (PLP) in glycogen phosphorylase. Biochemistry 35(47):15057–15064. https://doi.org/10.1021/bi9606004
Tang XW, Hsu CC, Schloss JV, Faiman MD, Wu E, Yang CY, Wu JY (1997) Protein phosphorylation and taurine biosynthesis in vivo and in vitro. J Neurosci 17(18):6947–6951
Taouji S, Higa A, Delom F, Palcy S, Mahon FX, Pasquet JM, Bosse R, Segui B, Chevet E (2013) Phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on tyrosine 164 inhibits its activity and promotes cell survival. J Biol Chem 288(24):17190–17201. https://doi.org/10.1074/jbc.M112.409185
Taylor SS, Kornev AP (2011) Protein kinases: evolution of dynamic regulatory proteins. Trends Biochem Sci 36(2):65–77. https://doi.org/10.1016/j.tibs.2010.09.006
Tehranian R, Montoya SE, Van Laar AD, Hastings TG, Perez RG (2006) Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells. J Neurochem 99(4):1188–1196. https://doi.org/10.1111/j.1471-4159.2006.04146.x
Tower DB (1976) GABA in nervous system function. Raven Press, New York
Vargas-Lopes C, Madeira C, Kahn SA, Albino do Couto I, Bado P, Houzel JC, De Miranda J, de Freitas MS, Ferreira ST, Panizzutti R (2011) Protein kinase C activity regulates d-serine availability in the brain. J Neurochem 116(2):281–290. https://doi.org/10.1111/j.1471-4159.2010.07102.x
Venerando A, Cesaro L, Pinna LA (2017) From phosphoproteins to phosphoproteomes: a historical account. FEBS J. https://doi.org/10.1111/febs.14014
Wei J, Wu JY (2008) Post-translational regulation of l-glutamic acid decarboxylase in the brain. Neurochem Res 33(8):1459–1465. https://doi.org/10.1007/s11064-008-9600-5
Wei J, Davis KM, Wu H, Wu JY (2004) Protein phosphorylation of human brain glutamic acid decarboxylase (GAD)65 and GAD67 and its physiological implications. Biochemistry 43(20):6182–6189. https://doi.org/10.1021/bi0496992
Wu JY, Tang XW, Schloss JV, Faiman MD (1998) Regulation of taurine biosynthesis and its physiological significance in the brain. Adv Exp Med Biol 442:339–345
Yard BA, Carter LG, Johnson KA, Overton IM, Dorward M, Liu H, McMahon SA, Oke M, Puech D, Barton GJ, Naismith JH, Campopiano DJ (2007) The structure of serine palmitoyltransferase; gateway to sphingolipid biosynthesis. J Mol Biol 370(5):870–886. https://doi.org/10.1016/j.jmb.2007.04.086
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This work was supported by FUR2016, University of Verona, to MB.
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Rossignoli, G., Phillips, R.S., Astegno, A. et al. Phosphorylation of pyridoxal 5′-phosphate enzymes: an intriguing and neglected topic. Amino Acids 50, 205–215 (2018). https://doi.org/10.1007/s00726-017-2521-3
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DOI: https://doi.org/10.1007/s00726-017-2521-3