Activation, regulation, and inhibition of DYRK1A

FEBS Journal

Volumn 278, Issue 2, 2011, Pages 246-256

  Becker, Walter ^a   Sippl, Wolfgang ^b  

^a RWTH AACHEN UNIVERSITY   (Germany)

^b MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

CMGC kinases; dual specificity; DYRK1A; harmine; INDY; kinase inhibitor; structural model; tyrosine autophosphorylation

Indexed keywords

DUAL SPECIFICITY TYROSINE PHOSPHORYLATION REGULATED KINASE 1A; HARMINE; PROTEIN INHIBITOR; PROTEIN KINASE; PURVALANOL A; PYRAZOLIDINE 3,5 DIONE 18; PYRAZOLIDINE 3,5 DIONE 21; TYROSINE; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; BINDING SITE; BRAIN; DROSOPHILA; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; GENE TRANSLOCATION; HOMOZYGOSITY; HUMAN; MOLECULAR DYNAMICS; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DEPHOSPHORYLATION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

ANIMALS; ENZYME ACTIVATION; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES;

EID: 78651070244     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2010.07956.x     Document Type: Review

References (86)

1. Kentrup H, Becker W, Heukelbach J, Wilmes A, Schürmann A, Huppertz C, Kainulainen H, &, Joost HG, (1996) Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII. J Biol Chem 271, 3488-3495.
2. Himpel S, Panzer P, Eirmbter K, Czajkowska H, Sayed M, Packman LC, Blundell T, Kentrup H, Grötzinger J, Joost HG, et al. (2001) Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A. Biochem J 359, 497-505.
3. Guimera J, Casas C, Pucharcos C, Solans A, Domenech A, Planas AM, Ashley J, Lovett M, Estivill X, &, Pritchard MA, (1996) A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum Mol Genet 5, 1305-1310.
4. Tejedor F, Zhu XR, Kaltenbach E, Ackermann A, Baumann A, Canal I, Heisenberg M, Fischbach KF, &, Pongs O, (1995) Minibrain: a new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron 14, 287-301.
5. Hämmerle B, Elizalde C, Galceran J, Becker W, &, Tejedor FJ, (2003) The MNB/DYRK1A protein kinase: neurobiological functions and Down syndrome implications. J Neural Transm Suppl 67, 129-137.
6. Park J, Song WJ, &, Chung KC, (2009) Function and regulation of Dyrk1A: towards understanding Down syndrome. Cell Mol Life Sci 66, 3235-3240.
7. Ferrer I, Barrachina M, Puig B, Martinez de LM, Marti E, Avila J, &, Dierssen M, (2005) Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis 20, 392-400.
8. Hämmerle B, &, Tejedor FJ, (2010) MNB/DYRK1A: a multiple regulator of neuronal development. FEBS J 278, 223-235.
9. Wegiel J, Gong CX, &, Hwang YW, (2010) DYRK1A: the role in neurodegenerative diseases. FEBS J 278, 236-245.
10. Nolen B, Taylor S, &, Ghosh G, (2004) Regulation of protein kinases; controlling activity through activation segment conformation. Mol Cell 15, 661-675.
11. Johnson LN, Noble ME, &, Owen DJ, (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85, 149-158.
12. Ogawa Y, Nonaka Y, Goto T, Ohnishi E, Hiramatsu T, Kii I, Yoshida M, Ikura T, Onogi H, Shibuya H, et al. (2010) Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A. Nat Commun 1, 1-9.
13. Cole A, Frame S, &, Cohen P, (2004) Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event. Biochem J 377, 249-255.
14. Lochhead PA, Sibbet G, Morrice N, &, Cleghon V, (2005) Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell 121, 925-936.
15. Lochhead PA, Kinstrie R, Sibbet G, Rawjee T, Morrice N, &, Cleghon V, (2006) A chaperone-dependent GSK3beta transitional intermediate mediates activation-loop autophosphorylation. Mol Cell 24, 627-633.
16. Kinstrie R, Luebbering N, Miranda-Saavedra D, Sibbet G, Han J, Lochhead PA, &, Cleghon V, (2010) Characterization of a domain that transiently converts class 2 DYRKs into intramolecular tyrosine kinases. Sci Signal 3, ra16.
17. Göckler N, Jofre G, Papadopoulos C, Soppa U, Tejedor FJ, &, Becker W, (2009) Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation. FEBS J 276, 6324-6337.
18. Crews CM, Alessandrini AA, &, Erikson RL, (1991) Mouse Erk-1 gene product is a serine/threonine protein kinase that has the potential to phosphorylate tyrosine. Proc Natl Acad Sci USA 88, 8845-8849.
19. Seger R, Ahn NG, Boulton TG, Yancopoulos GD, Panayotatos N, Radziejewska E, Ericsson L, Bratlien RL, Cobb MH, &, Krebs EG, (1991) Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation. Proc Natl Acad Sci USA 88, 6142-6146.
20. Fu Z, Schroeder MJ, Shabanowitz J, Kaldis P, Togawa K, Rustgi AK, Hunt DF, &, Sturgill TW, (2005) Activation of a nuclear Cdc2-related kinase within a mitogen-activated protein kinase-like TDY motif by autophosphorylation and cyclin-dependent protein kinase-activating kinase. Mol Cell Biol 25, 6047-6064.
21. Fu Z, Larson KA, Chitta RK, Parker SA, Turk BE, Lawrence MW, Kaldis P, Galaktionov K, Cohn SM, Shabanowitz J, et al. (2006) Identification of yin-yang regulators and a phosphorylation consensus for male germ cell-associated kinase (MAK)-related kinase. Mol Cell Biol 26, 8639-8654.
22. Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, &, Han J, (2002) MAPKK-independent activation of p38alpha mediated by TAB 1-dependent autophosphorylation of p38alpha. Science 295, 1291-1294.
23. Adayev T, Chen-Hwang MC, Murakami N, Lee E, Bolton DC, &, Hwang YW, (2007) Dual-specificity tyrosine phosphorylation-regulated kinase 1A does not require tyrosine phosphorylation for activity in vitro. Biochemistry 46, 7614-7624.
24. Wiechmann S, Czajkowska H, de Graaf K, Grötzinger J, Joost HG, &, Becker W, (2003) Unusual function of the activation loop in the protein kinase DYRK1A. Biochem Biophys Res Commun 302, 403-408.
25. Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, &, Pearl LH, (2001) Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 105, 721-732.
26. Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, &, Pearl LH, (2003) Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J 22, 494-501.
27. MÃller RS, Kübart S, Hoeltzenbein M, Heye B, Vogel I, Hansen CP, Menzel C, Ullmann R, Tommerup N, Ropers HH, et al. (2008) Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly. Am J Hum Genet 82, 1165-1170.
28. Dierssen M, &, de Lagran MM, (2006) DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): a gene with dosage effect during development and neurogenesis. Sci World J 6, 1911-1922.
29. Kurabayashi N, Hirota T, Sakai M, Sanada K, &, Fukada Y, (2010) DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping. Mol Cell Biol 30, 1757-1768.
30. Maenz B, Hekerman P, Vela EM, Galceran J, &, Becker W, (2008) Characterization of the human DYRK1A promoter and its regulation by the transcription factor E2F1. BMC Mol Biol 9, 30.
31. Kim MY, Jeong BC, Lee JH, Kee HJ, Kook H, Kim NS, Kim YH, Kim JK, Ahn KY, &, Kim KK, (2006) A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells. Proc Natl Acad Sci USA 103, 13074-13079.
32. Kimura R, Kamino K, Yamamoto M, Nuripa A, Kida T, Kazui H, Hashimoto R, Tanaka T, Kudo T, Yamagata H, et al. (2007) The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease. Hum Mol Genet 16, 15-23.
33. Lee Y, Ha J, Kim HJ, Kim YS, Chang EJ, Song WJ, &, Kim HH, (2009) Negative feedback inhibition of NFATc1 by DYRK1A regulates bone homeostasis. J Biol Chem 284, 33343-33351.
34. Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, Neilson JR, Chen L, Heit JJ, Yamasaki N, et al. (2006) NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 441, 595-601.
35. Rechsteiner M, &, Rogers SW, (1996) PEST sequences and regulation by proteolysis. Trends Biochem Sci 21, 267-271.
36. Alvarez M, Altafaj X, Aranda S, &, de la Luna S, (2007) DYRK1A autophosphorylation on serine residue 520 modulates its kinase activity via 14-3-3 binding. Mol Biol Cell 18, 1167-1178.
37. Zou Y, Lim S, Lee K, Deng X, &, Friedman E, (2003) Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M. J Biol Chem 278, 49573-49581.
38. Skurat AV, &, Dietrich AD, (2004) Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein kinases. J Biol Chem 279, 2490-2498.
39. Morita K, Lo Celso C, Spencer-Dene B, Zouboulis CC, &, Watt FM, (2006) HAN11 binds mDia1 and controls GLI1 transcriptional activity. J Dermatol Sci 44, 11-20.
40. Mazmanian G, Kovshilovsky M, Yen D, Mohanty A, Mohanty S, Nee A, &, Nissen RM, (2010) The zebrafish dyrk1b gene is important for endoderm formation. Genesis 48, 20-30.
41. Komorek J, Kuppuswamy M, Subramanian T, Vijayalingam S, Lomonosova E, Zhao LJ, Mymryk JS, Schmitt K, &, Chinnadurai G, (2010) Adenovirus type 5 E1A and E6 proteins of low-risk cutaneous beta-human papillomaviruses suppress cell transformation through interaction with FOXK1/K2 transcription factors. J Virol 84, 2719-2731.
42. Li D, Jackson RA, Yusoff P, &, Guy GR, (2010) The direct association of sp routy-r elated p rotein with an E VH1 d omain (SPRED) 1 or SPRED2 with DYRK1A modifies substrate kinase interactions. J Biol Chem 285, 35374-35385.
43. Cheng KC, Klancer R, Singson A, &, Seydoux G, (2009) Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases EGG-4 and EGG-5 during the oocyte-to-embryo transition. Cell 139, 560-572.
44. Parry JM, Velarde NV, Lefkovith AJ, Zegarek MH, Hang JS, Ohm J, Klancer R, Maruyama R, Druzhinina MK, Grant BD, et al. (2009) EGG-4 and EGG-5 link events of the oocyte-to-embryo transition with meiotic progression in C. elegans. Curr Biol 19, 1752-1757.
45. Taira N, Nihira K, Yamaguchi T, Miki Y, &, Yoshida K, (2007) DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage. Mol Cell 25, 725-738.
46. Moriya H, Shimizu-Yoshida Y, Omori A, Iwashita S, Katoh M, &, Sakai A, (2001) Yak1p, a DYRK family kinase, translocates to the nucleus and phosphorylates yeast Pop2p in response to a glucose signal. Genes Dev 15, 1217-1228.
47. Galcerán J, de Graaf K, Tejedor FJ, &, Becker W, (2003) The MNB/DYRK1A protein kinase: genetic and biochemical properties. J Neural Transm Suppl 67, 139-148.
48. Mao J, Maye P, Kogerman P, Tejedor FJ, Toftgard R, Xie W, Wu G, &, Wu D, (2002) Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1. J Biol Chem 277, 35156-35161.
49. Woods YL, Rena G, Morrice N, Barthel A, Becker W, Guo S, Unterman TG, &, Cohen P, (2001) The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site. Biochem J 355, 597-607.
50. Becker W, &, Joost HG, (1999) Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity. Prog Nucleic Acid Res Mol Biol 62, 1-17.
51. Kannan N, &, Neuwald AF, (2004) Evolutionary constraints associated with functional specificity of the CMGC protein kinases MAPK, CDK, GSK, SRPK, DYRK, and CK2alpha. Protein Sci 13, 2059-2077.
52. Knight ZA, &, Shokat KM, (2007) Chemical genetics: where genetics and pharmacology meet. Cell 128, 425-430.
53. Kim ND, Yoon J, Kim JH, Lee JT, Chon YS, Hwang MK, Ha I, &, Song WJ, (2006) Putative therapeutic agents for the learning and memory deficits of people with Down syndrome. Bioorg Med Chem Lett 16, 3772-3776.
54. Savage MJ, &, Gingrich DE, (2009) Advances in the development of kinase inhibitor therapeutics for Alzheimer's disease. Drug Dev Res 70, 125-144.
55. Koo KA, Kim ND, Chon YS, Jung MS, Lee BJ, Kim JH, &, Song WJ, (2009) QSAR analysis of pyrazolidine-3,5-diones derivatives as Dyrk1A inhibitors. Bioorg Med Chem Lett 19, 2324-2328.
56. Scales TM, Lin S, Kraus M, Goold RG, &, Gordon-Weeks PR, (2009) Nonprimed and DYRK1A-primed GSK3 beta-phosphorylation sites on MAP1B regulate microtubule dynamics in growing axons. J Cell Sci 122, 2424-2435.
57. Seifert A, Allan LA, &, Clarke PR, (2008) DYRK1A phosphorylates caspase 9 at an inhibitory site and is potently inhibited in human cells by harmine. FEBS J 275, 6268-6280.
58. Bain J, McLauchlan H, Elliott M, &, Cohen P, (2003) The specificities of protein kinase inhibitors: an update. Biochem J 371, 199-204.
59. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, &, Cohen P, (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J 408, 297-315.
60. Tachibana H, Koga K, Fujimura Y, &, Yamada K, (2004) A receptor for green tea polyphenol EGCG. Nat Struct Mol Biol 11, 380-381.
61. Khan N, Afaq F, Saleem M, Ahmad N, &, Mukhtar H, (2006) Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3- gallate. Cancer Res 66, 2500-2505.
62. Bode AM, &, Dong Z, (2006) Molecular and cellular targets. Mol Carcinog 45, 422-430.
63. Lambert JD, Sang S, &, Yang CS, (2007) Biotransformation of green tea polyphenols and the biological activities of those metabolites. Mol Pharm 4, 819-825.
64. Canzonetta C, Mulligan C, Deutsch S, Ruf S, O'Doherty A, Lyle R, Borel C, Lin-Marq N, Delom F, Groet J, et al. (2008) DYRK1A-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome. Am J Hum Genet 83, 388-400.
65. Murakami N, Xie W, Lu RC, Chen-Hwang MC, Wieraszko A, &, Hwang YW, (2006) Phosphorylation of amphiphysin I by minibrain kinase/dual-specificity tyrosine phosphorylation-regulated kinase, a kinase implicated in Down syndrome. J Biol Chem 281, 23712-23724.
66. Shi J, Zhang T, Zhou C, Chohan MO, Gu X, Wegiel J, Zhou J, Hwang YW, Iqbal K, Grundke-Iqbal I, et al. (2008) Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome. J Biol Chem 283, 28660-28669.
67. Guedj F, Sébrié C, Rivals I, Ledru A, Paly E, Bizot JC, Smith D, Rubin E, Gillet B, Arbones M, et al. (2009) Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS ONE 4, e4606.
68. Kim H, Sablin SO, &, Ramsay RR, (1997) Inhibition of monoamine oxidase A by beta-carboline derivatives. Arch Biochem Biophys, 337, 137-142.
69. Callaway JC, McKenna DJ, Grob CS, Brito GS, Raymon LP, Poland RE, Andrade EN, Andrade EO, &, Mash DC, (1999) Pharmacokinetics of Hoasca alkaloids in healthy humans. J Ethnopharmacol 65, 243-256.
70. Waki H, Park KW, Mitro N, Pei L, Damoiseaux R, Wilpitz DC, Reue K, Saez E, &, Tontonoz P, (2007) The small molecule harmine is an antidiabetic cell-type-specific regulator of PPARgamma expression. Cell Metab 5, 357-370.
71. Park KW, Waki H, Villanueva CJ, Monticelli LA, Hong C, Kang S, MacDougald OA, Goldrath AW, &, Tontonoz P, (2008) Inhibitor of DNA binding 2 is a small molecule-inducible modulator of peroxisome proliferator-activated receptor-gamma expression and adipocyte differentiation. Mol Endocrinol 22, 2038-2048.
72. Laguna A, Aranda S, Barallobre MJ, Barhoum R, Fernandez E, Fotaki V, Delabar JM, de la LS, de la Villa P, &, Arbones ML, (2008) The protein kinase DYRK1A regulates caspase-9-mediated apoptosis during retina development. Dev Cell 15, 841-853.
73. Sitz JH, Baumgärtel K, Hämmerle B, Papadopoulos C, Hekerman P, Tejedor FJ, Becker W, &, Lutz B, (2008) The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4. Neuroscience 157, 596-605.
74. Kuhn C, Frank D, Will R, Jaschinski C, Frauen R, Katus HA, &, Frey N, (2009) DYRK1A is a novel negative regulator of cardiomyocyte hypertrophy. J Biol Chem 284, 17320-17327.
75. Pagano MA, Bain J, Kazimierczuk Z, Sarno S, Ruzzene M, Di Maira G, Elliott M, Orzeszko A, Cozza G, Meggio F, et al. (2008) The selectivity of inhibitors of protein kinase CK2: an update. Biochem J 415, 353-365.
76. Sarno S, Reddy H, Meggio F, Ruzzene M, Davies SP, Donella Deana A, Shugar D, &, Pinna LA, (2001) Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of protein kinase CK2 ('casein kinase-2'). FEBS Lett 496, 44-48.
77. Muraki M, Ohkawara B, Hosoya T, Onogi H, Koizumi J, Koizumi T, Sumi K, Yomoda J, Murray MV, Kimura H, et al. (2004) Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem 279, 24246-24254.
78. Mott BT, Tanega C, Shen M, Maloney DJ, Shinn P, Leister W, Marugan JJ, Inglese J, Austin CP, Misteli T, et al. (2009) Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk). Bioorg Med Chem Lett 19, 6700-6705.
79. Adayev T, Chen-Hwang MC, Murakami N, Wegiel J, &, Hwang YW, (2006) Kinetic properties of a MNB/DYRK1A mutant suitable for the elucidation of biochemical pathways. Biochemistry 45, 12011-12019.
80. Pierantoni GM, Fedele M, Pentimalli F, Benvenuto G, Pero R, Viglietto G, Santoro M, Chiariotti L, &, Fusco A, (2001) High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth. Oncogene 20, 6132-6141.
81. Miyata Y, Akashi M, &, Nishida E, (1999) Molecular cloning and characterization of a novel member of the MAP kinase superfamily. Genes Cells 4, 299-309. (Pubitemid 29287632)
82. Hughes K, Nikolakaki E, Plyte SE, Totty NF, &, Woodgett JR, (1993) Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J 12, 803-808.
83. Bertani I, Rusconi L, Bolognese F, Forlani G, Conca B, De Monte L, Badaracco G, Landsberger N, &, Kilstrup-Nielsen C, (2006) Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation. J Biol Chem 281, 32048-32056.
84. Abe MK, Kahle KT, Saelzler MP, Orth K, Dixon JE, &, Rosner MR, (2001) ERK7 is an autoactivated member of the MAPK family. J Biol Chem 276, 21272-21279.
85. Klevernic IV, Stafford MJ, Morrice N, Peggie M, Morton S, &, Cohen P, (2006) Characterization of the reversible phosphorylation and activation of ERK8. Biochem J 394, 365-373.
86. Chang L, &, Karin M, (2001) Mammalian MAP kinase signalling cascades. Nature 410, 37-40.