Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments
Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments
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DOI：
10.1038/ni.2116
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发表时间：
2011-11-01
影响因子：
30.5
通讯作者：
Pierce, Susan K.
中科院分区：
文献类型：
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作者：
Chaturvedi, Akanksha;Martz, Rebecca;Pierce, Susan K.
抗原与B细胞抗原受体（BCR）的结合触发BCR信号传导和内吞作用。内吞作用如何调节BCR信号转导仍然是未知的。在这里，我们报告说，BCR信号并没有被BCR的内吞作用所消除;相反，在质膜上启动的BCR信号继续随着BCR在细胞内的连续磷酸化激酶而被运输。阻断BCR的内吞作用导致近端和下游激酶募集到质膜，其中促分裂原活化蛋白激酶（MAPK）过度磷酸化，激酶Akt及其下游靶点Foxo磷酸化不足，导致由这些途径控制的基因转录失调。因此，BCR的细胞定位用于区室化激酶活化以调节信号传导的结果。
Binding of antigen to the B cell antigen receptor (BCR) triggers both BCR signaling and endocytosis. How endocytosis regulates BCR signaling remains unknown. Here we report that BCR signaling was not extinguished by endocytosis of BCRs; instead, BCR signaling initiated at the plasma membrane continued as the BCR trafficked intracellularly with the sequential phosphorylation of kinases. Blocking the endocytosis of BCRs resulted in the recruitment of both proximal and downstream kinases to the plasma membrane, where mitogen-activated protein kinases (MAPKs) were hyperphosphorylated and the kinase Akt and its downstream target Foxo were hypophosphorylated, which led to the dysregulation of gene transcription controlled by these pathways. Thus, the cellular location of the BCR serves to compartmentalize kinase activation to regulate the outcome of signaling.