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Cell Growth & Differentiation Vol. 12, 481-486, September 2001
© 2001 American Association for Cancer Research

Involvement of p38 Kinase in Hydroxyurea-induced Differentiation of K562 Cells1

Joo-In Park2, Hee-Sun Choi, Jin-Sook Jeong, Jin-Yeong Han and In-Hoo Kim

Institute of Medical Science and Departments of Biochemistry [J-I. P., H-S. C.], Pathology [J-S. J.], and Clinical Pathology [J-Y. H.], Dong-A University College of Medicine, Busan 602-103, Korea, and Department of Molecular and Cellular Biology [I-H. K.], Baylor College of Medicine, Houston, Texas 77030

Hydroxyurea is a differentiation-inducing agent of human erythroleukemia K562 cells. However, the cellular mechanisms by which hydroxyurea exerts its effects on tumor cells, leading to the inhibition of cell growth and the induction of differentiation markers, are largely unknown. This study examined the role of different mitogen-activated protein kinase signal transduction pathways in hydroxyurea-induced erythroid differentiation of K562 cells. Using a panel of anti-extracellular signal-related kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 phosphospecific antibodies, we demonstrated that phosphorylation of ERK and JNK is decreased after the treatment of cells with hydroxyurea, whereas phosphorylation of p38 is increased. Moreover, inhibition of ERK activity by PD98059 induced erythroid differentiation, and it acted synergistically with hydroxyurea on hemoglobin synthesis, whereas inhibition of p38 activity by SB203580 inhibited induction of hemoglobin production by hydroxyurea. These findings suggest that the activation of p38 kinase may play important roles in the signal transduction mechanisms of hydroxyurea leading to erythroid differentiation.




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2001 by the American Association of Cancer Research.