Ca2+ influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells
Ca2+ influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells
复制标题
DOI：
10.1242/jcs.061051
复制
发表时间：
2010-03-15
影响因子：
4
通讯作者：
Mori, Yasuo
中科院分区：
文献类型：
--
作者：
Numaga, Takuro;Nishida, Motohiro;Mori, Yasuo
由产生肌醇1，4，5-三磷酸[Ins（1，4，5）P-3]和二酰基甘油（DAG）的磷脂酶C介导的Ca 2+信号传导控制淋巴细胞活化。与Ins（1，4，5）P-3诱导的内质网Ca ~（2+）释放激活的钙库操作的Ca ~（2+）内流不同，DAG激活的Ca ~（2+）内流的重要性仍然不清楚。在这里，我们描述了DAG激活的Ca 2+进入通道在B细胞受体（BCR）信号转导中的生理作用。在禽类DT 40 B细胞中，质膜（PM）上瞬时受体电位TRPC 3的缺乏损害了DAG激活的阳离子电流，并且在BCR刺激后，蛋白激酶C β（PKC β）持续易位到PM，从而激活细胞外信号调节激酶（ERK）。值得注意的是，TRPC 3显示出与PKC β的直接关联，其维持PKC β在PM的定位。因此，TRPC 3在PM处作为Ca 2+可渗透通道和蛋白质支架，用于B细胞中的下游PKC β活化。
Ca2+ signaling mediated by phospholipase C that produces inositol 1,4,5-trisphosphate [Ins(1,4,5) P-3] and diacylglycerol (DAG) controls lymphocyte activation. In contrast to store-operated Ca2+ entry activated by Ins(1,4,5)P-3-induced Ca2+ release from endoplasmic reticulum, the importance of DAG-activated Ca2+ entry remains elusive. Here, we describe the physiological role of DAG-activated Ca2+ entry channels in B-cell receptor (BCR) signaling. In avian DT40 B cells, deficiency of transient receptor potential TRPC3 at the plasma membrane (PM) impaired DAG-activated cation currents and, upon BCR stimulation, the sustained translocation to the PM of protein kinase C beta (PKC beta) that activated extracellular signal-regulated kinase (ERK). Notably, TRPC3 showed direct association with PKC beta that maintained localization of PKC beta at the PM. Thus, TRPC3 functions as both a Ca2+-permeable channel and a protein scaffold at the PM for downstream PKC beta activation in B cells.