Although MAP kinase (MAPK) has been shown to phosphorylate and activate cPLA2, the generality for such a role of MAPK in regulating cPLA2 is yet unproved. In MDCK-D1 cells, we observed a phosphatasesensitive increase in cPLA2 activity in lysates prepared from bradykinintreated cells, suggesting that a kinase-mediated phosphorylation is involved in the regulation of cPLA2 by bradykinin. However, bradykinin failed to activate MAPK, as determined by measuring the activity and molecular weight shift of MAPK- As a positive control, both epinephrine and phorbol ester increased enzyme activity and the molecular weight shift of MAPK. Treatment with the protein kinase C (PKC) inhibitor GFI09203X abolished phorbol ester-, but not bradykinin-, promoted arachidonic acid release. These data suggest that neither MAPK nor PKC is involved in the regulation of cPLA2 by bradykinin receptors in MDCK-D1 cells In contrast, MAPK is involved in the activation of cPLA2 by epinephrine since epinephrine-promoted AA release was inhibited by the MAPK cascade inhibitor PD098059. In spite of the differential involvement of MAPK, we observed similar extent of cPLA2 activation by bradykinin and epinephrine. We conclude that MAPK and PKC are not necessary for cPLA2 activation by bradykinin (and perhaps other agonists) and that different G protein-coupled receptors appear to phosphorylate and activate cPLA2 through different pathways.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology