Activation of protein kinase C and phospholipase A2 by phorbol diester in Madin Darby canine kidney cells
The authors report that in Madin Darby canine kidney (MDCK) cells activation of protein kinase C by TPA correlates with activation of a phospholipase A2. Exposure of MDCK cells to TPA induced protein kinase C translocation from the cytosol to the particulate fraction of the cells and stimulated the phosphorylation of proteins of 40,000 and 48,000 daltons. The dose response and time course for stimulation of protein phosphorylation by TPA was similar to that for the activation of a phospholipase A2. Two compounds which inhibit protein kinase C by different mechanisms inhibited activation of protein kinase C in MDCK cells. Both 1-octadecyl-2-methoxy-glycero-3-phosphocholine (ET-18-OCH3) and 1-(5-isoquinolinesulfonyl)piperazine inhibited protein kinase C from MDCK cells and inhibited the TPA stimulation of protein phosphorylation in the intact cells. Either compound inhibited the release of arachidonic acid from phospholipids induced by TPA and consequently decreased prostaglandin synthesis. Phospholipase A2 was not directly inhibited since ET-18-OCH3 failed to inhibit A23187 induced arachidonic acid release. Other studies showed that the ability of the cells to convert arachidonic acid into prostaglandins was not effects by the ET-18-OCH3. Thus, activation of protein kinase C by TPA causes the activation of a phospholipase A2 involved in arachidonic acid release in the MDCK cells.
- Research Organization:
- Wake Forest Univ., Winston-Salem, NC
- OSTI ID:
- 6279535
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ARACHIDONIC ACID
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CARCINOGENS
CATS
CHEMICAL REACTIONS
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
ESTERASES
ESTERS
HYDROLASES
INHIBITION
KIDNEYS
LIPASE
LIPIDS
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHORBOL ESTERS
PHOSPHOLIPIDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROSTAGLANDINS
PROTEINS
SYNTHESIS
TRANSFERASES
VERTEBRATES