Activation of c-Jun N-terminal kinase (JNK) by lysophosphatidic acid in Swiss 3T3 fibroblasts

Lysophosphatidic acid (LPA) induced activation of c-Jun N-terminal kinase (JNK) in Swiss 3T3 fibroblasts. This activation reached the maximum at 20 min and required a high concentration of LPA with an EC50 value of approximately 3 mu g/ml. LPA-induced activation of JNK was not suppressed by prior treatment of the cells with pertussis toxin, whereas it was completely blocked by suramin, a non-selective inhibitor of ligand-receptor interactions. The kinetics and concentration-dependency of LPA-induced JNK activation were in sharp contrast with those of LPA-induced extracellular signal-regulated kinase (ERK) activation, which reached the maximum within 3 min and occurred with an EC50 of 0.1 mu g/ml. The ERK activation was susceptible to pertussis toxin, whereas it was not inhibited by suramin. These results indicate that the signal transduction pathways of LPA-induced JNK and ERK activations are distinct. Thus, this is the first report showing that LPA induces not only ERK activation but also JNK activation, which may be responsible for the induction of DNA synthesis in LPA-stimulated Swiss 3T3 fibroblasts.