title: The role of protein kinase C in arachidonic acid release and prostaglandin E production from CHO cells transfected with EGF receptors.
abstract: Arachidonic acid release and prostaglandin production are stimulated by both phorbol esters and growth factors in various cell types. Whereas phorbol esters activate and transmit a signal via protein kinase C, this pathway is not necessarily involved in growth factor signal transduction. We investigated the involvement of protein kinase C in the pathway of arachidonic acid metabolism by CHO cells transfected with full-length EGF receptor (CHOwt). Two isoforms of protein kinase C were identified in CHOwt cells, alpha and zeta. On downregulation, the parallel loss of phorbol ester-stimulated arachidonic acid release and the alpha-isoform suggests a possible involvement of this isoform in phospholipase A2 activation in these cells. In addition, we propose that the zeta-isoform may be separately involved in prostaglandin production as residual phorbol ester-stimulation of PGE production occurs in downregulated cells where PKC zeta is the sole remaining isoform. EGF stimulation of arachidonic acid release, as a measure of phospholipase A2 activation, and subsequent prostaglandin production are unaffected by inhibition of protein kinase C in CHOwt cells. Indeed one such inhibitor, staurosporine, augmented the EGF effect. These results suggest that PKC is not required for EGF activation of phospholipase A2 in these cells.
authors.affiliation: University of Melbourne, Department of Medicine, PO Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Clark
authors.forename: R
authors.initials: R
authors.lastname: Keogh
authors.forename: M
authors.initials: M
authors.lastname: Dunlop
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects* / Q000235:genetics; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D000470:Alkaloids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate