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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2838-2846
REDK, a novel human regulatory erythroid
kinase
Kenneth A. Lord,
Caretha L. Creasy,
Andrew G. King,
Caroline King,
Brian M. Burns,
John C. Lee, and
Susan B. Dillon
From SmithKline Beecham Pharmaceuticals, Collegeville, PA.
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.

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