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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3579-3584
HEMATOPOIESIS
Fibronectin- and protein kinase C-mediated activation of
ERK/MAPK are essential for proplateletlike formation
Fang Jiang,
Yuzhi Jia, and
Isaac Cohen
From the Department of Cell and Molecular Biology and
the Department of Pathology, Northwestern University, Chicago, IL.
The megakaryoblastic CHRF-288 cell line was used to investigate
signal transduction pathways responsible for proplateletlike formation
(PPF). The role of fibronectin (FN) and protein kinase C (PKC)
activation in PPF were examined. In the presence of serum and phorbol
12-myristate 13-acetate (PMA), a PKC activator, cells exhibited full
megakaryocytic differentiation, manifested by adhesion, shape change,
increased cell size, polyploidy, PPF, and expression of
CD41+, CD61+, and CD62P+.
The same morphologic and phenotypic features were observed in serum-free cultures in the presence of FN/PMA. Only partial
differentiation occurred when other integrin ligands were
substituted for FN. FN alone induced minimal cell adhesion and
spreading, while PMA alone induced only polyploidy without adhesion.
Signal transduction changes involved the activation of the
extracellular signal-regulated protein kinase 1 (ERK1)/ERK2 as well as
c-Jun amino-terminal kinase 1 (JNK1)/stress-activated protein kinase
(SAPK). Phosphoinositide-3 kinase and p38 were not stimulated
under these conditions. Inhibitors were used to identify the causal
relationship between signaling pathways and PPF. PD98059 and
GF109203X, inhibitors of ERK1/ERK2 pathway and PKC,
respectively, blocked PPF, while adhesion, spreading, and polyploidy
were normal. These studies show that activation of ERK1/ERK2
mitogen-activated protein kinase pathway plays a critical role in PPF.
The elucidation of the signal transduction pathway on megakaryocyte
development and PPF is of crucial importance for understanding this
unique biological process.
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