cd14226

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1

CDD entry
Member databaseCDD
CDD typedomain
Short namePKc_DYRK1
SetPKc_like

Description

Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
[15, 31, 8, 29, 16, 9, 1, 19, 4, 17, 13, 10, 12, 30, 21, 27, 25, 3, 20, 5, 18, 11, 28, 14, 32, 6, 7, 26, 2, 33, 22, 24, 23]

References

1.The MNB/DYRK1A protein kinase: neurobiological functions and Down syndrome implications. Hammerle B, Elizalde C, Galceran J, Becker W, Tejedor FJ. J Neural Transm Suppl 129-37, (2003). PMID: 15068245

2.Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1. Mao J, Maye P, Kogerman P, Tejedor FJ, Toftgard R, Xie W, Wu G, Wu D. J Biol Chem 277, 35156-61, (2002). PMID: 12138125

3.The protein kinase DYRK1A regulates caspase-9-mediated apoptosis during retina development. Laguna A, Aranda S, Barallobre MJ, Barhoum R, Fernandez E, Fotaki V, Delabar JM, de la Luna S, de la Villa P, Arbones ML. Dev Cell 15, 841-53, (2008). PMID: 19081073

4.DYRK1B-dependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS. Lauth M, Bergstrom A, Shimokawa T, Tostar U, Jin Q, Fendrich V, Guerra C, Barbacid M, Toftgard R. Nat Struct Mol Biol 17, 718-25, (2010). PMID: 20512148

5.Dyrk1A overexpression in immortalized hippocampal cells produces the neuropathological features of Down syndrome. Park J, Yang EJ, Yoon JH, Chung KC. Mol Cell Neurosci 36, 270-9, (2007). PMID: 17720532

6.Regulation of the proapoptotic activity of huntingtin interacting protein 1 by Dyrk1 and caspase-3 in hippocampal neuroprogenitor cells. Kang JE, Choi SA, Park JB, Chung KC. J Neurosci Res 81, 62-72, (2005). PMID: 15906374

7.Mirk/dyrk1B kinase destabilizes cyclin D1 by phosphorylation at threonine 288. Zou Y, Ewton DZ, Deng X, Mercer SE, Friedman E. J Biol Chem 279, 27790-8, (2004). PMID: 15075324

8.Mirk/Dyrk1B in cancer. Friedman E. J. Cell. Biochem. 102, 274-9, (2007). View articlePMID: 17583556

9.The MNB/DYRK1A protein kinase: genetic and biochemical properties. Galceran J, de Graaf K, Tejedor FJ, Becker W. J Neural Transm Suppl 139-48, (2003). PMID: 15068246

10.DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping. Kurabayashi N, Hirota T, Sakai M, Sanada K, Fukada Y. Mol. Cell. Biol. 30, 1757-68, (2010). View articlePMID: 20123978

11.Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas. Mercer SE, Ewton DZ, Shah S, Naqvi A, Friedman E. Cancer Res 66, 5143-50, (2006). PMID: 16707437

12.Negative feedback Inhibition of NFATc1 by DYRK1A regulates bone homeostasis. Lee Y, Ha J, Kim HJ, Kim YS, Chang EJ, Song WJ, Kim HH. J Biol Chem 284, 33343-51, (2009). PMID: 19801542

13.The zebrafish dyrk1b gene is important for endoderm formation. Mazmanian G, Kovshilovsky M, Yen D, Mohanty A, Mohanty S, Nee A, Nissen RM. Genesis 48, 20-30, (2010). PMID: 20014342

14.The survival kinase Mirk/dyrk1B is activated through Rac1-MKK3 signaling. Jin K, Lim S, Mercer SE, Friedman E. J Biol Chem 280, 42097-105, (2005). PMID: 16257974

15.Function and regulation of Dyrk1A: towards understanding Down syndrome. Park J, Song WJ, Chung KC. Cell. Mol. Life Sci. 66, 3235-40, (2009). View articlePMID: 19685005

16.Mirk/Dyrk1B: a multifunctional dual-specificity kinase involved in growth arrest, differentiation, and cell survival. Mercer SE, Friedman E. Cell Biochem Biophys 45, 303-15, (2006). PMID: 16845176

17.Dyrk1A-mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer's disease. Ryu YS, Park SY, Jung MS, Yoon SH, Kwen MY, Lee SY, Choi SH, Radnaabazar C, Kim MK, Kim H, Kim K, Song WJ, Chung SH. J Neurochem 115, 574-84, (2010). PMID: 20456003

18.The survival kinase Mirk/Dyrk1B is a downstream effector of oncogenic K-ras in pancreatic cancer. Jin K, Park S, Ewton DZ, Friedman E. Cancer Res 67, 7247-55, (2007). PMID: 17671193

19.Dyrk1A phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. Park J, Oh Y, Yoo L, Jung MS, Song WJ, Lee SH, Seo H, Chung KC. J Biol Chem 285, 31895-906, (2010). PMID: 20696760

20.Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome. Liu F, Liang Z, Wegiel J, Hwang YW, Iqbal K, Grundke-Iqbal I, Ramakrishna N, Gong CX. FASEB J 22, 3224-33, (2008). PMID: 18509201

21.Mirk/Dyrk1B, a novel therapeutic target, mediates cell survival in non-small cell lung cancer cells. Gao J, Zheng Z, Rawal B, Schell MJ, Bepler G, Haura EB. Cancer Biol Ther 8, 1671-9, (2009). PMID: 19633423

22.Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome. Guimera J, Casas C, Estivill X, Pritchard M. Genomics 57, 407-18, (1999). PMID: 10329007

23.Differing substrate specificities of members of the DYRK family of arginine-directed protein kinases. Campbell LE, Proud CG. FEBS Lett 510, 31-6, (2002). PMID: 11755526

24.Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases. Becker W, Weber Y, Wetzel K, Eirmbter K, Tejedor FJ, Joost HG. J Biol Chem 273, 25893-902, (1998). PMID: 9748265

25.DYRK1A is a novel negative regulator of cardiomyocyte hypertrophy. Kuhn C, Frank D, Will R, Jaschinski C, Frauen R, Katus HA, Frey N. J Biol Chem 284, 17320-17327, (2009). PMID: 19372220

26.DYRK1 is a co-activator of FKHR (FOXO1a)-dependent glucose-6-phosphatase gene expression. von Groote-Bidlingmaier F, Schmoll D, Orth HM, Joost HG, Becker W, Barthel A. Biochem Biophys Res Commun 300, 764-9, (2003). PMID: 12507516

27.Attenuation of Notch signalling by the Down-syndrome-associated kinase DYRK1A. Fernandez-Martinez J, Vela EM, Tora-Ponsioen M, Ocana OH, Nieto MA, Galceran J. J Cell Sci 122, 1574-83, (2009). PMID: 19383720

28.The kinase Mirk/Dyrk1B mediates cell survival in pancreatic ductal adenocarcinoma. Deng X, Ewton DZ, Li S, Naqvi A, Mercer SE, Landas S, Friedman E. Cancer Res 66, 4149-58, (2006). PMID: 16618736

29.DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): a gene with dosage effect during development and neurogenesis. Dierssen M, de Lagran MM. ScientificWorldJournal 6, 1911-22, (2006). PMID: 17205196

30.Age-associated motor and visuo-spatial learning phenotype in Dyrk1A heterozygous mutant mice. Arque G, de Lagran MM, Arbones ML, Dierssen M. Neurobiol Dis 36, 312-9, (2009). PMID: 19660545

31.Two key genes closely implicated with the neuropathological characteristics in Down syndrome: DYRK1A and RCAN1. Park J, Oh Y, Chung KC. BMB Rep 42, 6-15, (2009). PMID: 19192387

32.Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Ferrer I, Barrachina M, Puig B, Martinez de Lagran M, Marti E, Avila J, Dierssen M. Neurobiol Dis 20, 392-400, (2005). PMID: 16242644

33.Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells. Yang EJ, Ahn YS, Chung KC. J Biol Chem 276, 39819-24, (2001). PMID: 11518709

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