ACTIVATION OF ERK AND JNK1 MAP KINASES IN CULTURED LUNG-TISSUE

Activation of ERK and JNK1 MAP kinases in cultured lung tissue. Am. J. Physiol. 273 (Lung Cell. Mol. Physiol. 17): L459-L467, 1997.-The bioc hemical mechanisms responsible for lung cell growth and proliferation are not well defined during tissue injury. We previously showed stimul ation of DNA synthesis in intact lung tissue cultured in vitro after e xposure to elevated fractions of O-2. By use of this in vitro model, t he current study examined the enzymatic activities of the extracellula r-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-a ctivated protein (MAP) kinase pathways. ERK and JNK activities were tr ansiently elevated in lung tissue cultured under serum-free conditions . Raf-l kinase, the primary upstream activator of the ERK pathway, was also transiently activated, suggesting a receptor-mediated ERK activa tion. Phosphorylation of the guanine nucleotide exchange protein p170 son of sevenless further suggested a receptor-mediated activation of t he ERK pathway. c-Fos and c-Jun expression, downstream targets of ERK and JNK, was dramatically increased in cultured tissue compared with u ncultured tissue. After the initial transient activation, ERK and JNK could be reactivated with specific agonists, demonstrating that these signaling pathways were functional. These findings demonstrate activat ion of the ERK and JNK MAP kinase pathways in intact lung tissue and p rovide a model system to define signaling pathways involved in lung ti ssue remodeling injury.