Activation of Epstein-Barr virus/C3d receptor (gp140, CR2, CD21) on human cell surface triggers pp60src and Akt-GSK3 activities upstream and downstream to PI 3-kinase, respectively
Activation of Epstein-Barr virus/C3d receptor (gp140, CR2, CD21) on human cell surface triggers pp60src and Akt-GSK3 activities upstream and downstream to PI 3-kinase, respectively
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DOI：
10.1002/eji.200324059
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发表时间：
2003-09-01
影响因子：
5.4
通讯作者：
Frade, R
中科院分区：
文献类型：
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作者：
Barel, M;Balbo, M;Frade, R
我们以前证明，人B淋巴细胞表面上的CR 2活化特异性地触发了95-kDa核仁素的酪氨酸磷酸化，这导致其与PI 3-激酶的p85亚基的SH 2结构域结合并激活该酶。CD 19和BCR均不能诱导正常B淋巴细胞核仁素的酪氨酸磷酸化，这清楚地证明了CR 2途径的特异性。这些数据使我们在本文中研究另外的分子事件，其由PI 3-激酶激活的上游和下游的CR2激活触发。在上游，我们证明pp 60 src，一个src家族的酪氨酸激酶，参与核仁素的酪氨酸磷酸化，而syk酪氨酸激酶没有。我们还证明了一个直接的蛋白质-蛋白质相互作用的pp 60 src与核仁素的CR2依赖性和CD 19非依赖性途径。下游，我们证明了CR2激活也触发Akt和GSK 3酶激活，该途径受pp 60 src酪氨酸激酶激活的控制。活化的CR2的这些调节功能是特异性的，独立于syk酪氨酸激酶和CD 19和BCR活化。因此，CR2激活募集特异性机制来激活PI 3-激酶及其后续途径，该机制不同于CD 19和BCR募集的机制。
We previously demonstrated that CR2 activation on human B lymphocyte surface specifically triggered tyrosine phosphorylation of the 95-kDa nucleolin, this leading to its binding on SH2 domains of p85 sub-unit of PI 3-kinase and to activation of this enzyme. The specificity of CR2 pathway was clearly demonstrated as neither CD19 nor BCR could induce tyrosine phosphorylation of nucleolin in normal B lymphocytes. These data led us to investigate herein additional molecular events, which were triggered by CR2 activation, upstream and downstream to PI 3-kinase activation. Upstream, we demonstrated that pp60src, a tyrosine kinase of the src family, was involved in tyrosine phosphorylation of nucleolin, while syk tyrosine kinase was not. We also demonstrated a direct protein-protein interaction of pp60src with nucleolin in a CR2-dependent and CD19-independent pathway. Downstream, we demonstrated that CR2 activation also triggered Akt and GSK3 enzyme activation, this pathway being under the control of pp60src tyrosine kinase activation. These regulatory functions of activated CR2 were specific as independent of syk tyrosine kinase and of CD19 and BCR activation. Thus, CR2 activation recruits a specific mechanism to activate PI 3-kinase and its subsequent pathways, this mechanism being different to those recruited by CD19 and BCR.