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Different roles of p38 MAPK and ERK in STI571‐induced multi‐lineage differentiation of K562 cells
Author(s) -
Kohmura Kanoko,
Miyakawa Yoshitaka,
Kawai Yoko,
Ikeda Yasuo,
Kizaki Masahiro
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10426
Subject(s) - k562 cells , mapk/erk pathway , biology , kinase , microbiology and biotechnology , p38 mitogen activated protein kinases , leukemia , immunology
Abstract STI571 is a specific tyrosine kinase inhibitor of Abl kinase. It was previously reported that STI571 induced hemoglobin synthesis in the chronic myelogenous leukemia (CML) cell line K562. However, its mechanisms remain unknown. In this study, we demonstrated that STI571 induced the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and dephosphorylation of extracellular signal‐regulated kinase (ERK) in K562 cells. In contrast, the phosphorylation of c‐Jun N‐terminal kinases (JNK) in K562 cells was not altered by STI571. We also found that STI571 induced all the myeloid (CD11b, CD13), megakaryocytic (CD41a, CD42), and erythroid (glycophorin‐A) markers on K562 cells. A p38 MAPK‐specific inhibitor, SB203580, inhibited the STI571‐induced multi‐lineage differentiation of K562 cells, indicating that p38 MAPK is crucial for this differentiation. In contrast, SB203580 did not overcome the inhibitory effect for proliferation of K562 cells, indicating that p38 MAPK activation by STI571 does not affect cell numbers. Among the hematopoietic transcription factors, the expression level of c‐myb mRNA was clearly downregulated after incubation with STI571 in K562 cells. STI571‐induced downregulation of c‐myb mRNA was prevented by the pretreatment of K562 cells by SB203580. Our data provides insights into how p38 MAPK and ERK pathways are involved in STI571‐induced differentiation of K562 cells. J. Cell. Physiol. 198: 370–376, 2004© 2003 Wiley‐Liss, Inc.