+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases



Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases



Journal of Biological Chemistry 273(40): 25893-25902



DYRK1 is a dual specificity protein kinase presumably involved in brain development. Here we show that the kinase belongs to a new family of protein kinases comprising at least seven mammalian isoforms (DYRK1A, DYRK1B, DYRK1C, DYRK2, DYRK3, DYRK4A, and DYRK4B), the yeast homolog Yak1p, and the Drosophila kinase minibrain (MNB). In rat tissues, DYRK1A is expressed ubiquitously, whereas transcripts for DYRK1B, DYRK2, DYRK3, and DYRK4 were detected predominantly in testes of adult but not prepuberal rats. By fluorescence microscopy and subcellular fractionation, a green fluorescent protein (GFP) fusion protein of DYRK1A was found to accumulate in the nucleus of transfected COS-7 and HEK293 cells, whereas GFP-DYRK2 was predominantly detected in the cytoplasm. DYRK1A exhibited a punctate pattern of GFP fluorescence inside the nucleus and was co-purified with the nuclear matrix. Analysis of GFP-DYRK1A deletion constructs showed that the nuclear localization of DYRK1A was mediated by its nuclear targeting signal (amino acids 105-139) but that its characteristic subnuclear distribution depended on additional N-terminal elements (amino acids 1-104). When expressed in Escherichia coli, DYRK1A, DYRK2, DYRK3, MNB, and Yak1p catalyzed their autophosphorylation on tyrosine residues. The kinases differed in their substrate specificity in that DYRK2 and DYRK3, but not DYRK1A and MNB, catalyzed phosphorylation of histone H2B. The heterogeneity of their subcellular localization and substrate specificity suggests that the kinases are involved in different cellular functions.

(PDF emailed within 0-6 h: $19.90)

Accession: 009399322

Download citation: RISBibTeXText

PMID: 9748265

DOI: 10.1074/jbc.273.40.25893


Related references

Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity. Progress in Nucleic Acid Research and Molecular Biology 62: 1-17, 1999

Unveiling the novel dual specificity protein kinases in Bacillus anthracis: identification of the first prokaryotic dual specificity tyrosine phosphorylation-regulated kinase (DYRK)-like kinase. Journal of Biological Chemistry 287(32): 26749-26763, 2012

Structural Optimization and Pharmacological Evaluation of Inhibitors Targeting Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases (DYRK) and CDC-like kinases (CLK) in Glioblastoma. Journal of Medicinal Chemistry 60(5): 2052-2070, 2017

Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk). Bioorganic and Medicinal Chemistry Letters 21(10): 3152-3158, 2011

Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) exert a strong anti-herpesviral activity. Antiviral Research 143: 113-121, 2017

A novel phosphatase family, structurally related to dual-specificity phosphatases, that displays unique amino acid sequence and substrate specificity. Journal of Molecular Biology 374(4): 899-909, 2007

Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: development of chemical probe ML315. Bioorganic and Medicinal Chemistry Letters 23(12): 3654-3661, 2014

Evolutionary constraints associated with functional specificity of the CMGC protein kinases MAPK, CDK, GSK, SRPK, DYRK, and CK2alpha. Protein Science 13(8): 2059-2077, 2004

Different domains of the mitogen-activated protein kinases ERK3 and ERK2 direct subcellular localization and upstream specificity in vivo. Journal of Biological Chemistry 277(7): 5094-5100, 2001

Differing substrate specificities of members of the DYRK family of arginine-directed protein kinases. FEBS Letters 510(1-2): 31-36, 2 January, 2002

The Downs syndrome candidate gene DYRK1 is a member of a new family of dual specificity protein kinases. Naunyn-Schmiedeberg's Archives of Pharmacology 357(4 SUPPL): R66, 1998

Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe. Journal of Cell Science 111: 1635-1647, 1998

Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1. Journal of Medicinal Chemistry 51(17): 5229-5242, 2008

Common in vitro substrate specificity and differential Src homology 2 domain accessibility displayed by two members of the Src family of protein-tyrosine kinases, c-Src and Hck. Journal of Biological Chemistry 273(27): 16756-16763, 1998

Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases. Pharmacology & Therapeutics 100(2): 119-139, 2003