EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains
EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains
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DOI：
10.1016/s0896-6273(00)80706-0
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发表时间：
1999-03-01
期刊：
影响因子：
16.2
通讯作者：
Klein, R
中科院分区：
文献类型：
--
作者：
Brückner, K;Labrador, JP;Klein, R
跨膜ephrinB蛋白在胚胎模式形成过程中具有重要功能，它作为Eph受体酪氨酸激酶的配体，并且可能作为类似信号转导受体的分子。与“反向”信号传导一致，ephrinB1定位在富含鞘脂/胆固醇的脂筏微区，这是信号分子局部浓缩和激活的平台。谷氨酸受体相互作用蛋白（GRIP）以及一种我们称为GRIP2的高度相关蛋白，通过与ephrinB1的C末端PDZ靶位点结合而被招募到这些脂筏中。用可溶性EphB2受体胞外结构域刺激ephrinB1会导致形成大的脂筏斑块，其中也包含GRIP蛋白。此外，一种与GRIP相关的丝氨酸/苏氨酸激酶活性被招募到ephrinB1 - GRIP复合物中。我们的研究结果表明，GRIP蛋白为ephrinB配体下游的多蛋白信号复合物的组装提供了一个支架。
Transmembrane ephrinB proteins have important functions during embryonic patterning as ligands for Eph receptor tyrosine kinases and presumably as signal-transducing receptor-like molecules. Consistent with "reverse" signaling, ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains, platforms for the localized concentration and activation of signaling molecules. Glutamate receptor-interacting protein (GRIP) and a highly related protein, which we have termed GRIP2, are recruited into these rafts through association with the c-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble EphB2 receptor ectodomain causes the formation of large raft patches that also contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands.