Distinct phospholipase C-regulated signalling pathways in Swiss 3T3 fibroblasts induce the rapid generation of the same polyunsaturated diacylglycerols.
Prostaglandin F2alpha, platelet-derived growth factor (PDGF) and calcium ionophore A23187 stimulated the rapid (within 25 s) generation of polyunsaturated 1,2-diacylglycerol (DAG) species, in particular 18:0/20:3n-9, 18:0/20:4n-6 and 18:0/20:5n-3, in Swiss 3T3 fibroblasts. This was followed by a second sustained phase characterised by saturated, monounsaturated and diunsaturated DAG species derived, at least partially, from a phospholipase D/phosphatidate phosphohydrolase-linked pathway. This could be directly activated by phorbol ester. Assay of rat brain protein kinase C (PKC) in lipid vesicles showed that first phase, polyunsaturated-enriched DAG isolated from Swiss 3T3 cells was a more potent activator of kinase activity compared to that achieved with DAG from control or 5 min stimulated cells. Thus activation of distinct members of the phospholipase C family leads to the rapid and almost identical generation of polyunsaturated DAG species which are capable of preferentially activating protein kinase C (PKC).
Pettitt
T R
TR
Institute for Cancer Studies, University of Birmingham Medical School, Birmingham, UK.
Wakelam
M J
MJ
D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000201:enzymology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis* / Q000737:chemistry; D015237:Dinoprost / Q000494:pharmacology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D007476:Ionophores; D010713:Phosphatidylcholines; D010982:Platelet-Derived Growth Factor; D000001:Calcimycin; D015237:Dinoprost; D010711:Phosphatidate Phosphatase; D010738:Type C Phospholipases; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium