Regulation of phosphatidic acid phosphohydrolase by epidermal growth factor. Reduced association with the EGF receptor followed by increased association with protein kinase Cepsilon.
An important component of receptor-mediated intracellular signal transduction is the generation of lipid second messengers. Lipid second messenger production is a complex process involving a variety of regulatory enzymes that control the intracellular response to the extracellular signal. Phosphatidic acid (PA) is generated in response to phospholipase D and can be converted to other lipid second messengers including diacylglycerol (DG) and lysophosphatidic acid. PA is converted to DG by PA phosphohydrolase (PAP). We report here that PAP activity can be detected in epidermal growth factor (EGF) receptor immunoprecipitates. Following treatment with EGF, there is a substantial reduction in the PAP activity that co-precipitates with the EGF receptor. The loss of EGF receptor-associated PAP activity occurs with a concomitant increase in PAP activity associated with the epsilon isoform of protein kinase C (PKC). The PAP activity associated with PKCepsilon was dependent upon the PKC co-factors phosphatidylserine and DG but was independent of the kinase activity of PKCepsilon. These data suggest a novel signaling mechanism for the regulation of lipid second messenger production and implicate PAP as an important regulatory component for lipid second messenger production in receptor-mediated intracellular signaling.
Jiang
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Y
Department of Biological Sciences, The Hunter College of the City University of New York, New York, New York 10021, USA. foster@genectr.hunter.cuny.edu
Lu
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Z
Zang
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Q
Foster
D A
DA
D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*
D007527:Isoenzymes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C; D010711:Phosphatidate Phosphatase; D005033:Ethylmaleimide