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Blood, 15 February 2001, Vol. 97, No. 4, pp. 901-910
HEMATOPOIESIS
mDYRK3 kinase is expressed selectively in late erythroid
progenitor cells and attenuates colony-forming unit-erythroid
development
Justin N. Geiger,
Geoffry
T. Knudsen,
Leigh Panek,
Ajay K. Pandit,
Michael D. Yoder,
Kenneth A. Lord,
Caretha L. Creasy,
Brian M. Burns,
Peter Gaines,
Susan B. Dillon, and
Don M. Wojchowski
From the Departments of Biochemistry & Molecular
Biology and Veterinary Science, The Pennsylvania State
University, University Park, PA; SmithKline-Beecham Pharmaceuticals,
Collegeville, PA; and SmithKline-Beecham Pharmaceuticals, King of
Prussia, PA.
DYRKs are a new subfamily of dual-specificity kinases that was
originally discovered on the basis of homology to Yak1, an inhibitor of
cell cycle progression in yeast. At present, mDYRK-3 and mDYRK-2 have
been cloned, and mDYRK-3 has been characterized with respect to kinase
activity, expression among tissues and hematopoietic cells, and
possible function during erythropoiesis. In sequence, mDYRK-3 diverges
markedly in noncatalytic domains from mDYRK-2 and mDYRK-1a, but is
91.3% identical overall to hDYRK-3. Catalytically, mDYRK-3 readily
phosphorylated myelin basic protein (but not histone 2B) and
also appeared to autophosphorylate in vitro. Expression of mDYRK-1a,
mDYRK-2, and mDYRK-3 was high in testes, but unlike mDYRK1a and mDYRK
2, mDYRK-3 was not expressed at appreciable levels in other tissues
examined. Among hematopoietic cells, however, mDYRK-3 expression was
selectively elevated in erythroid cell lines and primary pro-erythroid
cells. In developmentally synchronized erythroid progenitor cells,
expression peaked sharply following exposure to erythropoietin plus
stem cell factor (SCF) (but not SCF alone), and in situ hybridizations
of sectioned embryos revealed selective expression of mDYRK-3 in fetal
liver. Interestingly, antisense oligonucleotides to mDYRK-3 were shown
to significantly and specifically enhance colony-forming
unit-erythroid colony formation. Thus, it is proposed that mDYRK-3
kinase functions as a lineage-restricted, stage-specific suppressor of
red cell development.

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