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

Received 20 July 2001; accepted 11 March 2002.

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.

Abbreviations: 8Br-cAMP, 8-bromoadenosine-3′,5′-cyclic-monophosphate, ERK, extracellular signal-regulated kinase, MEK, mitogen-activated protein kinase, PKA, protein kinase A, TPA, phorbol 12-myristate 13-acetate

Keywords: Cyclic AMP, Extracellular signal-regulated kinase, B-Raf, Protein kinase A, Differentiation, HL-60 cells

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

b Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, South Korea

Corresponding author. Tel.: +82-2-590-1202; fax: +82-2-536-2485.

PII: S0145-2126(02)00057-7

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