DYRK family of protein kinases: evolutionary relationships, biochemical properties, and functional roles

Aranda, Sergi; Laguna, Ariadna; Luna, Susana de la

doi:10.1096/fj.10-165837

Cited by 284 publications

(357 citation statements)

References 102 publications

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“…4a,b), which is also likely to be an essential kinase (Table 1) and is related to the pre-mRNA processing kinase hPRP4 found in higher eukaryotes 4 . Phylogenetic analysis shows that these two kinases belong to a cluster that also includes the DYRKs sub-family 4,29 . The DYRKs are serine/threonine kinases of the CMGC kinase family that are characterized by the formation of an active transient intermediate during translation that is able to catalyse cis-auto-phosphorylate on tyrosine 29,30 .…”

Section: Resultsmentioning

confidence: 99%

Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum

et al. 2011

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The role of protein phosphorylation in the life cycle of malaria parasites is slowly emerging. Here we combine global phospho-proteomic analysis with kinome-wide reverse genetics to assess the importance of protein phosphorylation in Plasmodium falciparum asexual proliferation. We identify 1177 phosphorylation sites on 650 parasite proteins that are involved in a wide range of general cellular activities such as DnA synthesis, transcription and metabolism as well as key parasite processes such as invasion and cyto-adherence. several parasite protein kinases are themselves phosphorylated on putative regulatory residues, including tyrosines in the activation loop of PfGsK3 and PfCLK3; we show that phosphorylation of PfCLK3 Y526 is essential for full kinase activity. A kinome-wide reverse genetics strategy identified 36 parasite kinases as likely essential for erythrocytic schizogony. These studies not only reveal processes that are regulated by protein phosphorylation, but also define potential anti-malarial drug targets within the parasite kinome.

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Section: Resultsmentioning

confidence: 99%

Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum

et al. 2011

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“…31 No relevant functional redundancy of the different DYRK members has been reported. 1,32 The Dyrk1a (± ) mouse is a phenocopy of the human phenotype. The pyramidal cells of the cerebral cortex are considerably smaller, less branched and less spinous in the cortex of Dyrk1A ± mice than in normal mice, causing the neurons to receive fewer excitatory GABA and glutamatergic inputs.…”

Section: Discussionmentioning

confidence: 99%

“…1 Dual-specificity tyrosine phosphorylationregulated kinase 1A (DYRK1A) (MIM 600855) is a protein kinase located in the Down syndrome critical region (DSCR) of chromosome 21, and is a member of the highly conserved DYRK family of kinases. 1,2 DYRK proteins are dual-specificity kinases, which catalyze the phosphorylation of serine and threonine residues on exogenous substrates, as well as the phosphorylation of tyrosine residues in their own activation loop.…”

Section: Introductionmentioning

confidence: 99%

DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies

et al. 2015

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Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from − 2 SD to − 5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broadbased gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs.

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“…Dyrk2 belongs to a serine/threonine protein kinase family (26), implying that Dyrk2 might phosphorylate TERT protein and lead to degradation. To address this, we examined whether Dyrk2's kinase activity is required for TERT protein destabilization.…”

Section: Dyrk2-induced Tert Ubiquitination and Degradation-tomentioning

confidence: 99%

Dyrk2-associated EDD-DDB1-VprBP E3 Ligase Inhibits Telomerase by TERT Degradation

Jung

Wang

Jun

et al. 2013

Journal of Biological Chemistry

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Background:Telomerase is an essential enzyme for the immortalization of stem and cancer cells. Results: Dyrk2-associated E3 ligase targets telomerase reverse transcriptase, a catalytic subunit of telomerase. Conclusion: Dyrk2-E3 ligase is necessary to negatively regulate telomerase activity. Significance: Learning how telomerase is regulated is crucial for understanding telomerase regulatory mechanism in cancer and stem cells.

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DYRK family of protein kinases: evolutionary relationships, biochemical properties, and functional roles

Cited by 284 publications

References 102 publications

Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum

Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum

DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies

Dyrk2-associated EDD-DDB1-VprBP E3 Ligase Inhibits Telomerase by TERT Degradation

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