Brückner K, Pablo Labrador J, Scheiffele P, Herb A, Seeburg P H, Klein R
Developmental Biology Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Neuron. 1999 Mar;22(3):511-24. doi: 10.1016/s0896-6273(00)80706-0.
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.
跨膜ephrinB蛋白作为Eph受体酪氨酸激酶的配体，在胚胎模式形成过程中具有重要功能，并且可能作为信号转导受体样分子发挥作用。与“反向”信号传导一致，ephrinB1定位于富含鞘脂/胆固醇的脂筏微区，这些微区是信号分子局部聚集和激活的平台。谷氨酸受体相互作用蛋白（GRIP）和一种高度相关的蛋白（我们将其命名为GRIP2）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受体胞外域刺激ephrinB1会导致形成也包含GRIP蛋白的大脂筏斑块。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配体下游多蛋白信号复合物的组装提供了一个支架。
