Pertussis toxin signals through the TCR to initiate cross-desensitization of the chemokine receptor CXCR4.
Pertussis toxin signals through the TCR to initiate cross-desensitization of the chemokine receptor CXCR4.
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DOI：
10.4049/jimmunol.0803114
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发表时间：
2009-05-01
期刊：
影响因子：
--
通讯作者：
Miller WE
中科院分区：
文献类型：
--
作者：
Schneider OD;Weiss AA;Miller WE
百日咳毒素（PTx）已被证明对免疫细胞产生多种影响，而不依赖于其对adp核苷化G蛋白的能力。在这些作用中，PTx的结合亚基（PTxB）已被证明可以阻断通过趋化因子受体CCR5的信号传导，但这一过程的机制尚不清楚。在这里，我们发现PTxB引起相关趋化因子受体CXCR4的脱敏，并探索其发生的机制。CXCR4是趋化因子基质细胞衍生因子1α (SDF-1α)的受体，并引发许多生物学效应，包括刺激T细胞迁移。PTxB处理导致CXCR4表面表达降低，抑制G蛋白相关信号，阻断sdf -1α介导的趋化作用。我们发现PTxB通过激活TCR信号网络介导这些作用，因为这些作用依赖于TCR和ZAP70的表达。此外，用抗cd3单抗激活TCR会对CXCR4活性产生类似的影响，这支持了TCR信号传导导致CXCR4交叉脱敏的观点。PTxB对CXCR4的抑制是快速和短暂的；然而，PTx的催化活性长期阻止CXCR4信号转导。因此，PTx全毒素对CXCR4信号转导的影响可分为两个阶段：短期由B亚基作用，长期由催化亚基作用。这些数据表明，TCR与CXCR4的串扰可能是导致交叉脱敏的正常细胞过程，PTx的B亚基利用了交叉脱敏。
Pertussis toxin (PTx) has been shown to exert a variety of effects on immune cells independent of its ability to ADP-ribosylate G proteins. Of these effects, the binding subunit of PTx (PTxB) has been shown to block signaling via the chemokine receptor CCR5, but the mechanism involved in this process is unknown. Here, we show that PTxB causes desensitization of a related chemokine receptor, CXCR4, and explore the mechanism by which this occurs. CXCR4 is the receptor for the chemokine stromal cell-derived factor 1α (SDF-1α) and elicits a number of biological effects, including stimulation of T cell migration. PTxB treatment causes a decrease in CXCR4 surface expression, inhibits G protein-associated signaling, and blocks SDF-1α-mediated chemotaxis. We show that PTxB mediates these effects by activating the TCR signaling network, as the effects are dependent on TCR and ZAP70 expression. Additionally, the activation of the TCR with anti-CD3 mAb elicits a similar set of effects on CXCR4 activity, supporting the idea that TCR signaling leads to cross-desensitization of CXCR4. The inhibition of CXCR4 by PTxB is rapid and transient; however, the catalytic activity of PTx prevents CXCR4 signaling in the long term. Thus, the effects of PTx holotoxin on CXCR4 signaling can be divided into two phases: short term by the B subunit, and long term by the catalytic subunit. These data suggest that TCR crosstalk with CXCR4 is likely a normal cellular process that leads to cross-desensitization, which is exploited by the B subunit of PTx.
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影响因子：
5.4
作者：
DApuzzo, M;Rolink, A;Moser, B
通讯作者：
Moser, B
影响因子：
11.2
作者：
Geay, JF;Buet, D;Lonache, F
通讯作者：
Lonache, F
DOI：
10.1073/pnas.94.5.1925
发表时间：
1997-03-04
影响因子：
11.1
作者：
Bleul, CC;Wu, LJ;Mackay, CR
通讯作者：
Mackay, CR
B 细胞抗原受体结合抑制基质细胞衍生因子 (SDF)-1α 趋化性并促进蛋白激酶 C (PKC) 诱导的 CXCR4 内化。
DOI：
10.1084/jem.189.9.1461
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guinamard R;Signoret N;Ishiai M;Marsh M;Kurosaki T;Ravetch JV
通讯作者：
Ravetch JV
影响因子：
4.8
作者：
Fernandis, AZ;Cherla, RP;Ganju, RK
通讯作者：
Ganju, RK