Oxidant-dependent phosphorylation of p40phox in B lymphocytes
Oxidant-dependent phosphorylation of p40phox in B lymphocytes
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DOI：
10.1006/bbrc.2001.5665
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发表时间：
2001-10-05
影响因子：
3.1
通讯作者：
Vignais, PV
中科院分区：
文献类型：
--
作者：
Grandvaux, N;Elsen, S;Vignais, PV
与中性粒细胞NADPH氧化酶一样，B淋巴细胞NADPH氧化酶由膜结合的黄细胞色素B b和调节因子（包括Rac和胞质phox蛋白三联体p67 phox、p47 phox和p40 phox）组成。在这里，我们证明了磷酸化氨基酸分析和使用的有效的PKC抑制剂GFX，在刺激的B淋巴细胞与原钒酸钠和H2 O2，p40 phox组分的胞质phox三联体选择性磷酸化丝氨酸和苏氨酸残基的PKC型蛋白激酶。p40 phox磷酸化的模式与B淋巴细胞的主要PKC同种型PKC-δ的酪氨酸磷酸化动力学密切相关。染料木黄酮阻断H2 O2依赖的PKC酪氨酸磷酸化导致p40 phox磷酸化的抑制。PKC-δ的酪氨酸磷酸化和p40 phox的丝氨酸/苏氨酸磷酸化之间的相关性，以及PKC-δ的选择性抑制剂rottlerin对p40 phox磷酸化的抑制，使得活化的PKC-δ在B细胞中p40 phox的氧化剂依赖性磷酸化过程中成为可能的候选者。(C)北京：科学出版社.
As with the neutrophil NADPH oxidase, the B lymphocyte NADPH oxidase consists of a membrane-bound flavocytochrome b and regulatory factors including Rac and the cytosolic phox protein triad p67phox, p47phox, and p40phox. Here we demonstrate by phosphoamino acid analysis and the use of the potent PKC inhibitor GFX that, in response to stimulation of B lymphocytes with sodium orthovanadate and H2O2, the p40phox component of the cytosolic phox triad is selectively phosphorylated on serine and threonine residues by a PKC-type protein kinase. The pattern of p40phox phosphorylation was closely related to the kinetics of tyrosine phosphorylation of PKC-delta, the main PKC isotype of B lymphocytes. Blocking H2O2-dependent tyrosine phosphorylation of PKC by genistein resulted in inhibition of p40phox phosphorylation. The correlation between the tyrosine phosphorylation of PKC-delta and the serine/threonine phosphorylation of p40phox, together with the inhibition of p40phox phosphorylation by rottlerin, a selective inhibitor of PKC-delta, makes the activated PKC-delta a likely candidate in the process of the oxidant-dependent phosphorylation of p40phox in B cells. (C) 2001 Academic Press.