REDK, a novel human regulatory erythroid kinase.
We have identified a novel regulatory erythroid kinase (REDK) that is homologous to a family of dual-specificity kinases. The yeast homolog of REDK negatively regulates cell division, suggesting a similar function for REDK, which is primarily localized in the nucleus. REDK is present in hematopoietic tissues, such as bone marrow and fetal liver, but the RNA is expressed at significant levels only in erythroid or erythropoietin (EPO)-responsive cells. Two novel forms of cDNA (long and short) for REDK have been isolated that appear to be alternative splice products and imply the presence of polypeptides with differing amino termini. The ratio of short-to-long forms of REDK increases dramatically in CD34(+) cells cultured with EPO, suggesting differing regulation and function for each form. REDK is predominantly found in nuclear, rather than cytoplasmic, protein extracts, and immunoprecipitated REDK is active in phosphorylating histones H2b, H3, myelin basic protein, and other coimmunoprecipitated proteins. Antisense REDK oligonucleotides promote erythroid colony formation by human bone marrow cells, without affecting colony-forming unit (CFU)-GM, CFU-G, or CFU-GEMM numbers. Maximal numbers of CFU-E and burst-forming unit-erythroid were increased, and CFU-E displayed increased sensitivity to suboptimal EPO concentrations. The data indicate that REDK acts as a brake to retard erythropoiesis. (Blood. 2000;95:2838-2846)
Lord
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KA
SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426, USA. kenneth_a_lord@sbphrd.com
Creasy
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CL
King
A G
AG
King
C
C
Burns
B M
BM
Lee
J C
JC
Dillon
S B
SB
D000595:Amino Acid Sequence; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003114:Colony-Forming Units Assay; D005333:Fetus; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D013873:Thionucleotides; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D020319:Oligodeoxyribonucleotides, Antisense; D011994:Recombinant Proteins; D013873:Thionucleotides; C408131:DYRK3 protein, human; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases