Secretory phospholipase A(2) inhibits epidermal growth factor-induced receptor activation.
Secretory phospholipase A(2) (sPLA(2)) plays important roles in mediating various cellular processes, including cell proliferation, differentiation, apoptosis, and inflammatory response. In this study, we demonstrated that a basic sPLA(2) inhibits epidermal growth factor (EGF)-induced EGF receptor activation, as determined by autophosphorylation of EGF receptor, EGF-activated phospholipase D (PLD) activity, and phospholipase C-gamma(1) (PLC-gamma(1)) tyrosine phosphorylation in a human epidermoid carcinoma cell line, A-431. Treatment of cells with exogenous neutral sphingomyelinase (SMase) or a cell permeable ceramide analog, C(2)-ceramide, also caused similar inhibitory effects on EGF-induced activation of EGF receptor, tyrosine phosphorylation of PLC-gamma(1), and the activation of PLD. sPLA(2)-induced inhibition of EGF receptor was associated with arachidonic acid release, which was followed by an increase in intracellular ceramide formation. Both sPLA(2) and exogenous C(2)-ceramide are able to inhibit the proliferation of A-431. The data presented indicate for the first time that sPLA(2) downregulates the EGF receptor-mediated intracellular signal transduction that may be mediated by arachidonic acid and/or ceramide.
Zhao
Sheng
S
Laboratory of Molecular Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Box 25, 320 Yue-Yang Road, Shanghai, 200031, Peoples' Republic of China.
Du
Xiao-Yan
XY
Chen
Jun-Song
JS
Zhou
Yuan-cong
YC
Song
Jian-Gou
JG
D016718:Arachidonic Acid / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051966:Phospholipase C gamma; D010739:Phospholipase D / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D011868:Radioisotopes / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D002518:Ceramides; D007527:Isoenzymes; D011868:Radioisotopes; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D010741:Phospholipases A; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase; D051966:Phospholipase C gamma; D010739:Phospholipase D