Secretory phospholipase A(2) inhibits epidermal growth factor-induced receptor activation.
Secretory phospholipase A(2) inhibits epidermal growth factor-induced receptor activation.
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DOI：
10.1006/excr.2002.5622
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发表时间：
2002-10
影响因子：
3.7
通讯作者：
Sheng Zhao;Xiao-Yan Du;Jun-Song Chen;Yuan‐cong Zhou;Jianguo Song
中科院分区：
文献类型：
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作者：
Sheng Zhao;Xiao-Yan Du;Jun-Song Chen;Yuan‐cong Zhou;Jianguo Song
分泌型磷脂酶A（2）（sPLA（2））在介导细胞增殖、分化、凋亡和炎症反应等多种细胞过程中发挥重要作用。在这项研究中，我们证明了碱性sPLA（2）抑制表皮生长因子（EGF）诱导的EGF受体激活，如通过人表皮样癌细胞系A-431中EGF受体的自磷酸化、EGF激活的磷脂酶D（PLD）活性和磷脂酶C-γ（1）（PLC-γ（1））酪氨酸磷酸化所确定的。用外源性中性鞘磷脂酶（SMase）或细胞渗透性神经酰胺类似物C（2）-神经酰胺处理细胞，也对EGF诱导的EGF受体激活、PLC-γ（1）酪氨酸磷酸化和PLD激活产生类似的抑制作用。sPLA（2）诱导的EGF受体抑制与花生四烯酸释放有关，花生四烯酸释放后细胞内神经酰胺形成增加。sPLA（2）和外源性C（2）-神经酰胺均能抑制A-431细胞的增殖。所提供的数据首次表明sPLA（2）下调EGF受体介导的细胞内信号转导，该信号转导可能由花生四烯酸和/或神经酰胺介导。
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.