The Adaptor Protein 3BP2 Binds Human CD244 and Links this Receptor to Vav Signaling, ERK Activation, and NK Cell Killing1
The Adaptor Protein 3BP2 Binds Human CD244 and Links this Receptor to Vav Signaling, ERK Activation, and NK Cell Killing1
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接头蛋白 3BP2 结合人 CD244 并将该受体与 Vav 信号传导、ERK 激活和 NK 细胞杀伤联系起来1
DOI：
10.4049/jimmunol.175.7.4226
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Margarita Martín
中科院分区：
文献类型：
--
作者：
I. Saborit;J. D. Del Valle;X. Romero;E. Esplugues;P. Lauzurica;P. Engel;Margarita Martín
衔接蛋白是介导分子间相互作用的分子，对细胞活化至关重要。衔接子3BP 2已显示出正调节NK细胞介导的细胞毒性。在这项研究中，我们提出了3BP 2和CD 244受体之间的物理相互作用的证据。CD 244是CD 150家族的成员，是在NK、CD 8 + T和骨髓细胞上表达的细胞表面蛋白。CD 244通过其Src同源2结构域与X连锁淋巴增生性疾病基因产物信号传导淋巴细胞活化分子相关蛋白（SAP）/SH 2结构域蛋白1A相互作用。3BP 2与人而非鼠CD 244相互作用。CD 244 - 3BP 2相互作用是直接的，并通过磷酸化调节，如酵母和NK细胞中的三杂交分析所示。CD 244上的Tyr 337是SAP/SH 2结构域蛋白1A结合的共有基序的一部分，对于3BP 2相互作用至关重要。虽然Tyr 337突变为苯丙氨酸消除了人3BP 2结合，但我们仍然观察到SAP缔合，表明该基序对于SAP募集不是必需的。CD 244连接诱导3BP 2磷酸化和Vav-1募集。在CD 244触发后，3BP 2的过表达导致ERK激活的幅度和持续时间增加。这种增强伴随着由于CD 244连接引起的细胞毒性的增加。然而，当比较正常和3BP 2转染的细胞时，未发现IFN-γ分泌的差异。这些结果表明，CD 244 - 3BP 2结合调节细胞溶解功能，但不调节IFN-γ释放，从而加强了以下假设：在人体中，CD 244介导的细胞毒性和IFN-γ释放涉及不同的NK途径。
Adaptor proteins, molecules that mediate intermolecular interactions, are crucial for cellular activation. The adaptor 3BP2 has been shown to positively regulate NK cell-mediated cytotoxicity. In this study we present evidence for a physical interaction between 3BP2 and the CD244 receptor. CD244, a member of the CD150 family, is a cell surface protein expressed on NK, CD8+ T, and myeloid cells. CD244 interacts via its Src homology 2 domain with the X-linked lymphoproliferative disease gene product signaling lymphocytic activation molecule-associated protein (SAP)/SH2 domain protein 1A. 3BP2 interacts with human but not murine CD244. CD244-3BP2 interaction was direct and regulated by phosphorylation, as shown by a three-hybrid analysis in yeast and NK cells. Tyr337 on CD244, part of a consensus motif for SAP/SH2 domain protein 1A binding, was critical for the 3BP2 interaction. Although mutation of Tyr337 to phenylalanine abrogated human 3BP2 binding, we still observed SAP association, indicating that this motif is not essential for SAP recruitment. CD244 ligation induced 3BP2 phosphorylation and Vav-1 recruitment. Overexpression of 3BP2 led to an increase in the magnitude and duration of ERK activation, after CD244 triggering. This enhancement was concomitant with an increase in cytotoxicity due to CD244 ligation. However, no differences in IFN-γ secretion were found when normal and 3BP2-transfected cells were compared. These results indicate that CD244-3BP2 association regulates cytolytic function but not IFN-γ release, reinforcing the hypothesis that, in humans, CD244-mediated cytotoxicity and IFN-γ release involve distinct NK pathways.
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影响因子：
56.9
作者：
REN, RB;MAYER, BJ;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
20.3
作者：
J. Sayós;M. Martín;A. Chen;M. Simarro;D. Howie;M. Morra;P. Engel;C. Terhorst
通讯作者：
J. Sayós;M. Martín;A. Chen;M. Simarro;D. Howie;M. Morra;P. Engel;C. Terhorst
影响因子：
4.4
作者：
Say贸s, J;Nguyen, KB;Terhorst, C
通讯作者：
Terhorst, C
人类自然杀伤细胞激活过程中的信号转导：磷酸肌醇的生成和环磷酸腺苷的调节。
DOI：
--
发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Windebank,KP;Abraham,RT;Powis,G;Olsen,RA;Barna,TJ;Leibson,PJ
通讯作者：
Leibson,PJ