Role of PKCα–p38MAPK–Giα axis in NADPH oxidase derived O2·--mediated activation of cPLA2 under U46619 stimulation in pulmonary artery smooth muscle cells

We have recently reported that treatment of bovine pulmonary artery smooth muscle cells with the thromboxane A2 mimetic, U46619 stimulated NADPH oxidase derived O2·- level, which subsequently caused marked increase in [Ca2+]i[17]. Herein, we demonstrated that O2·--mediated increase in [Ca2+]i stimulates an aprotinin sensitive proteinase activity, which proteolytically activates PKC-α under U46619 treatment to the cells. The activated PKC-α then phosphorylates p38MAPK and that subsequently caused Giα phosphorylation leading to stimulation of cPLA2 activity in the cell membrane.

► U46619 treatment to pulmonary smooth muscle cells stimulates cPLA2 in the membrane.
► The cPLA2 activation occurs via phosphorylation of Giα by PKCα activated p38MAPK.
► PKCα appears to be proteolytically activated by an aprotinin sensitive protease.
► The protease activation occurs via stimulation of NADPH oxidase derived O2·-.
► U46619 activates cPLA2 upon stimulating PKCα-p38MAPK-Giα axis by an increase in O2·-.