Phosphorylation of p42/44MAPK by Various Signal Transduction Pathways Activates Cytosolic Phospholipase A2to Variable Degrees

Abstract Arachidonic acid has been implicated to play a role in physiological and pathophysiological processes and is selectively released by the 85-kDa cytosolic phospholipase A2 (cPLA2). The activity of cPLA2 is regulated by calcium, translocating the enzyme to its substrate, and by phosphorylation by a mitogen-activated protein kinase (MAPK) family member and a MAPK-activated protein kinase. In this study, the signal transduction pathways in growth factor-induced phosphorylation of p42/44MAPK and cPLA2activation were investigated in Her14 fibroblasts. p42/44MAPK in response to epidermal growth factor was not only phosphorylated via the Raf-MEK pathway but mainly through protein kinase C (PKC) or a related or unrelated kinase in which the phosphorylated p42/44MAPK corresponded with cPLA2 activity. Serum-induced phosphorylation of p42/44MAPK also corresponded with cPLA2activity but is predominantly mediated via Raf-MEK and partly through PKC or a related or unrelated kinase. In contrast, activation of PKC by phorbol ester did not result in increased cPLA2 activity, while p42/44MAPK is phosphorylated, mainly via Raf-MEK and through MEK. Moreover, p42/44MAPK phosphorylation is present in quiescent and proliferating cells, and p42/44MAPK is entirely phosphorylated via Raf-MEK, but it only corresponds to cPLA2 activity in the former cells. Collectively, these data show that p42/44MAPK in proliferating, quiescent, and stimulated cells is phosphorylated by various signal transduction pathways, suggesting the activation of different populations of p42/44MAPK and cPLA2.