The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2
The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2
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DOI：
10.1038/ncb1592
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发表时间：
2007-06-01
影响因子：
21.3
通讯作者：
Philips, Mark R.
中科院分区：
文献类型：
--
作者：
Mor, Adam;Campi, Gabriele;Philips, Mark R.
T淋巴细胞上的抗原受体（T细胞受体; TCR）接合的结果是T细胞发育、选择和功能所需的Ras活化。淋巴细胞功能相关抗原-1（LFA-1）介导淋巴细胞粘附、免疫突触稳定和双向信号传导。使用荧光生物传感器，我们发现，TCR活化与或不与CD 28共刺激导致激活的Ras仅在高尔基体上，而与LFA-1共刺激诱导Ras激活的高尔基体和质膜上。Ras激活两个隔室需要RasGRP 1，钙和甘油二酯（DAG）调节的交换因子，但磷脂酶C（PLC）的活性只需要激活高尔基体。LFA-1的参与通过刺激磷脂酶D（PLD）增加质膜处的DAG水平。PLD 2和磷脂酸磷酸酶（PAP）是Ras在质膜上活化所必需的。因此，LFA-1通过PLD 2作用以重塑TCR下游的Ras活化模式。
Ras activation as a consequence of antigen receptor (T-cell receptor; TCR) engagement on T lymphocytes is required for T-cell development, selection and function. Lymphocyte function-associated antigen-1 (LFA-1) mediates lymphocyte adhesion, stabilization of the immune synapse and bidirectional signalling. Using a fluorescent biosensor we found that TCR activation with or without costimulation of CD28 led to activation of Ras only on the Golgi apparatus, whereas costimulation with LFA-1 induced Ras activation on both the Golgi and the plasma membrane. Ras activation on both compartments required RasGRP1, an exchange factor regulated by calcium and diacylglycerol (DAG), but phospholipase C ( PLC) activity was required only for activation on the Golgi. Engagement of LFA-1 increased DAG levels at the plasma membrane by stimulating phospholipase D (PLD). PLD2 and phosphatidic acid phosphatase (PAP) were required for Ras activation on the plasma membrane. Thus, LFA-1 acts through PLD2 to reshape the pattern of Ras activation downstream of the TCR.