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Phospholipase D activation regulates endothelin‐1 stimulation of phosphoinositide‐specific phospholipase C in SK‐N‐MC cells
Author(s) -
Challiss R.A.John,
Wilkes Lesley C.,
Patel Viral,
Purkiss John R.,
Boarder Michael R.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80161-m
Subject(s) - phospholipase d , protein kinase c , phospholipase c , stimulation , chemistry , phospholipase , endothelin 1 , inositol phosphate , diacylglycerol kinase , inositol , second messenger system , microbiology and biotechnology , signal transduction , biochemistry , endocrinology , biology , enzyme , receptor
Endothelin‐1 (ET‐1) is known to stimulate phospholipase C (PLC) activity in SK‐N‐MC human neuroblastoma/epithelioma cells: here we show that phospholipase D(PLD) is also stimulated. The generation of inositol 1,4,5‐trisphosphate (Ins(1,4,5)P 3 ) by ET‐1‐stimulated PLC was attenuated by protein kinase C (PKC) activation and enhanced by PKC inhibition. An enhancement of ET‐1‐stimulated Ins(1,4,5)P 3 accumulation was also seen when the product of PLD activity was either diverted into phosphatidyl butanol in the presence of butanol, or phosphatidate phosphohydrolase (PPH) activity was inhibited by dl ‐propranolol. We conclude that there is an inhibitory, PKC‐mediated, feedback loop in these cells which is dependent, in part, on the activation of PKC by product(s) of the PLD/PPH pathway. This provides a novel role for agonist‐stimulated PLD activation.