Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes
Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes
复制标题
DOI：
10.1038/ncb1279
复制
发表时间：
2005-08-01
影响因子：
21.3
通讯作者：
Higgins, CF
中科院分区：
文献类型：
--
作者：
Elliott, JI;Surprenant, A;Higgins, CF
磷脂酰丝氨酸（PS）暴露通常与凋亡和死亡细胞的去除相关。我们观察到，PS是暴露在组成性高水平的T淋巴细胞，表达低水平的跨膜酪氨酸磷酸酶CD 45 RB。CD 45被证明是PS易位的负调节剂，响应于各种信号，包括ATP受体P2 X的激活（7）。PS分布的变化被证明可以调节几种膜活性：通过P2 X（7）阳离子通道本身的Ca 2+和Na+摄取; P2 X（7）刺激归巢受体CD 62 L的脱落;以及多药转运蛋白P-糖蛋白活性的逆转。这些数据确定了PS分布变化在信号转导中的作用，快速调节几种膜蛋白的活性。这似乎是一种全有或全无的效应，协调每个细胞中靶蛋白的大多数或所有分子的活性。这些数据还提出了一种规避多药耐药性的新方法。
Phosphatidylserine (PS) exposure is normally associated with apoptosis and the removal of dying cells. We observed that PS is exposed constitutively at high levels on T lymphocytes that express low levels of the transmembrane tyrosine phosphatase CD45RB. CD45 was shown to be a negative regulator of PS translocation in response to various signals, including activation of the ATP receptor P2X(7). Changes in PS distribution were shown to modulate several membrane activities: Ca2+ and Na+ uptake through the P2X(7) cation channel itself; P2X(7)-stimulated shedding of the homing receptor CD62L; and reversal of activity of the multidrug transporter P-glycoprotein. The data identify a role for PS distribution changes in signal transduction, rapidly modulating the activities of several membrane proteins. This seems to be an all-or-none effect, coordinating the activity of most or all the molecules of a target protein in each cell. The data also suggest a new approach to circumventing multidrug resistance.