环磷酸腺苷诱导HL-60细胞中细胞外信号调节激酶的激活：在环磷酸腺苷诱导的分化中的作用。

Cyclic AMP induces activation of extracellular signal-regulated kinases in HL-60 cells: role in cAMP-induced differentiation.

作者信息

Cho Young-Jin, Kim Ju-Young, Jeong Seong-Whan, Lee Sang Bok, Kim Ok Nyu

机构信息

Department of Pharmacology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, 137-701, Seoul, South Korea.

出版信息

Leuk Res. 2003 Jan;27(1):51-6. doi: 10.1016/s0145-2126(02)00057-7.

DOI:10.1016/s0145-2126(02)00057-7

PMID:12479852

Abstract

It is well known that elevated intracellular cAMP induces growth arrest and the differentiation of HL-60 cells to neutrophil-like cells. The present study was designed to assess the regulation of the extracellular signal-regulated kinase (ERK) pathway by cAMP and its association with differentiation in HL-60 cells. We found that 8-bromoadenosine-3',5'-cyclic-monophosphate (8Br-cAMP)-induced the activation of ERK and mitogen-activated protein kinase (MEK), but inhibited B-Raf kinase via a protein kinase A (PKA)-mediated mechanism. Prolonged exposure to 8Br-cAMP increased the phorbol 12-myristate 13-acetate (TPA)-stimulated superoxide generation and CD14 expression that characterize the differentiation phenotype, which was blocked by MEK-1 inhibitor. These data suggest that cAMP-induced ERK activation is essential for the differentiation of HL-60 cells, independently of B-Raf.

摘要

众所周知，细胞内cAMP升高会诱导HL-60细胞生长停滞并分化为中性粒细胞样细胞。本研究旨在评估cAMP对细胞外信号调节激酶（ERK）通路的调控及其与HL-60细胞分化的关联。我们发现，8-溴腺苷-3',5'-环一磷酸（8Br-cAMP）诱导ERK和丝裂原活化蛋白激酶（MEK）的激活，但通过蛋白激酶A（PKA）介导的机制抑制B-Raf激酶。长时间暴露于8Br-cAMP会增加佛波酯12-肉豆蔻酸酯13-乙酸酯（TPA）刺激的超氧化物生成和CD14表达，这些是分化表型的特征，而MEK-1抑制剂可阻断这种现象。这些数据表明，cAMP诱导的ERK激活对于HL-60细胞的分化至关重要，且独立于B-Raf。