THE ROLE OF PROTEIN-KINASE-C IN ARACHIDONIC-ACID RELEASE AND PROSTAGLANDIN-E PRODUCTION FROM CHO CELLS TRANSFECTED WITH EGF RECEPTORS

Arachidonic acid release and prostaglandin production are stimulated b y both phorbol esters and growth factors in various cell types. Wherea s phorbol esters activate and transmit a signal via protein kinase C, this pathway is not necessarily involved in growth factor signal trans duction. We investigated the involvement of protein kinase C in the pa thway of arachidonic acid metabolism by CHO cells transfected with ful l-length EGF receptor (CHOwt). Two isoforms of protein kinase C were i dentified in CHOwt cells, alpha and zeta. On downregulation, the paral lel loss of phorbol ester-stimulated arachidonic acid release and the alpha-isoform suggests a possible involvement of this isoform in phosp holipase A(2) activation in these cells. In addition, we propose that the zeta-isaform may be separately involved in prostaglandin productio n as residual phorbol ester-stimulation of PGE production occurs in do wnregulated cells where PKC zeta is the sole remaining isoform. EGF st imulation of arachidonic acid release, as a measure of phospholipase A (2) activation, and subsequent prostaglandin production are unaffected by inhibition of protein kinase C in CHOwt cells. Indeed one such inh ibitor, staurosporine, augmented the EGF effect. These results suggest that PKC is not required for EGF activation of phospholipase A(2) in these cells.