HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.
HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.
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作者：
电压门控质子电流调节吞噬细胞中活性氧（ROS）的产生。在B细胞中，B细胞抗原受体（BCR）的刺激导致参与B细胞活化的ROS的产生，但质子通道的参与尚不清楚。我们在这里报告的电压门控质子通道HVCN 1与BCR复合物，并与激活后的BCR一起内化。BCR诱导的ROS生成在HVCN 1缺陷型B细胞中较低，这通过酪氨酸磷酸酶SHP-1的BCR依赖性氧化受损导致BCR信号转导减弱。这导致激酶Syk和Akt的激活减少，线粒体呼吸和糖酵解受损，体内抗体应答减少。我们的研究结果确定了质子通道在B细胞中的意外功能，并证明了ROS在BCR信号传导和下游代谢中的重要性。
Voltage-gated proton currents regulate generation of reactive oxygen species (ROS) in phagocytic cells. In B cells, stimulation of the B cell antigen receptor (BCR) results in the production of ROS that participate in B cell activation, but the involvement of proton channels is unknown. We report here that the voltage-gated proton channel HVCN1 associated with the BCR complex and was internalized together with the BCR after activation. BCR-induced generation of ROS was lower in HVCN1-deficient B cells, which resulted in attenuated BCR signaling via impaired BCR-dependent oxidation of the tyrosine phosphatase SHP-1. This resulted in less activation of the kinases Syk and Akt, impaired mitochondrial respiration and glycolysis, and diminished antibody responses in vivo. Our findings identify unanticipated functions for proton channels in B cells and demonstrate the importance of ROS in BCR signaling and downstream metabolism.
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DOI：
10.1084/jem.185.3.551
发表时间：
1997-02-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luther SA;Gulbranson-Judge A;Acha-Orbea H;MacLennan IC
通讯作者：
MacLennan IC
影响因子：
32.4
作者：
Cornall, RJ;Cyster, JG;Goodnow, CC
通讯作者：
Goodnow, CC
影响因子：
10.5
作者：
Gottlob, K;Majewski, N;Hay, N
通讯作者：
Hay, N
影响因子：
20.3
作者：
Doughty, Cheryl A.;Bleiman, Blair F.;Chiles, Thomas C.
通讯作者：
Chiles, Thomas C.
影响因子：
7
作者：
Boyd, Robert S.;Jukes-Jones, Rebekah;Cain, Kelvin
通讯作者：
Cain, Kelvin