SHIP modulates immune receptor responses by regulating membrane association of Btk
SHIP modulates immune receptor responses by regulating membrane association of Btk
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DOI：
10.1016/s1074-7613(00)80555-5
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发表时间：
1998-04-01
期刊：
影响因子：
32.4
通讯作者：
Ravetch, JV
中科院分区：
文献类型：
--
作者：
Bolland, S;Pearse, RN;Ravetch, JV
SHIP的膜募集负责Fc γ RIIB与BCR共连接产生的抑制信号。通过降低PIP 3的水平，SHIP通过PH结构域-磷酸肌醇脂质相互作用调节酪氨酸激酶Btk与膜的缔合。通过Fc γ RIIB共连接、SHIP的膜表达或PI 3 K的抑制（导致PIP 3水平降低的条件）对BCR信号传导的抑制被作为膜相关嵌合体的Btk的表达所抑制。相反，通过缺失SHIP增加PIP 3水平导致Btk与膜和高反应性BCR信号传导的结合增加。这些结果表明PIP 3在通过调节Btk定位从而调节钙流来调节B细胞刺激状态中的中心作用。
Membrane recruitment of SHIP is responsible for the inhibitory signal generated by Fc gamma RIIB coligation to the BCR. By reducing the level of PIP3, SHIP regulates the association of the tyrosine kinase Btk with the membrane through PH domain-phosphoinositol lipid interactions. Inhibition of BCR signaling by either Fc gamma RIIB coligation, membrane expression of SHIP, or inhibition of PI3K, conditions which result in decreased levels of PIP3, is suppressed by the expression of Btk as a membrane-associated chimera. Conversely, increasing PIP3 levels by deletion of SHIP results in increased Btk association with the membrane and hyperresponsive BCR signaling. These results suggest a central role for PIP3 in regulating the B cell stimulatory state by modulating Btk localization and thereby calcium fluxes.