Surfactant secretagogue activation of protein kinase C isoforms in cultured rat type II cells.
Several lung surfactant secretagogues are known to activate protein kinase C (PKC) in type II cells. Such agents include 12-O-tetradecanoylphorbol 13-acetate (TPA) and cell-permeable diacylglycerols that directly activate PKC. Other agents include ATP and UTP, which act at P2Y(2) receptors coupled to phosphoinositide-specific phospholipase C, activation of which leads to formation of diacylglycerols and consequent activation of PKC. Activation of PKC is associated with redistribution of enzyme from a cytosolic to a membrane fraction of the cell. We examined the PKC isomers that are translocated by ATP, UTP, TPA, and dioctanoylglycerol in cultured type II cells isolated from adult rats. PKC isoforms were identified by Western blotting using isoform-specific antibodies. Treatment of type II cells with ATP, UTP, TPA, and dioctanoylglycerol resulted in a significant redistribution of PKC-mu from cytosol to membrane. TPA and dioctanoylglycerol also activated PKC-alpha, -betaI, -betaII, -delta, and -eta, but those isoforms were not activated by ATP or UTP. The effects of TPA and dioctanoylglycerol on PKC-mu were more pronounced than those of the P2Y(2) agonists, and the effect of TPA was also more rapid than that of ATP. The data show that direct activators and agents that generate endogenous diacylglycerols have different PKC activation patterns. Because it is activated by different types of secretagogues, PKC-mu may have an important role in the physiological regulation of surfactant secretion.
Gobran
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LI
Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Rooney
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SA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D004075:Diglycerides; D007527:Isoenzymes; D011663:Pulmonary Surfactants; C044295:1,2-dioctanoylglycerol; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D014544:Uridine Triphosphate