Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5.
Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5.
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DOI：
10.1126/scisignal.2000081
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发表时间：
2009-02-10
影响因子：
7.3
通讯作者：
Segars JH
中科院分区：
文献类型：
--
作者：
Kino T;Takatori H;Manoli I;Wang Y;Tiulpakov A;Blackman MR;Su YA;Chrousos GP;DeCherney AH;Segars JH
细胞外高渗或渗透压，通常由跨质膜的盐和大分子浓度的差异引起，发生在淋巴器官和炎症部位。免疫细胞对渗透压应激的反应受活化T细胞核因子5（NFAT 5）的调节，NFAT 5是一种诱导高渗反应基因表达并刺激细胞因子产生的转录因子。我们报告说，鸟嘌呤核苷酸交换因子（GEF）Brx [也被称为蛋白激酶A锚定蛋白13（AKAP 13）]是必不可少的nfat 5的表达在响应渗透压，从而传递细胞外高渗信号，使脾B细胞的分化和免疫球蛋白的生产。这个过程需要p38丝裂原活化蛋白激酶（MAPK）和NFAT 5的活性，并涉及Brx和c-Jun N-末端激酶（JNK）相互作用蛋白4（JIP 4）之间的物理相互作用，JIP 4是一种特异性激活p38 MAPK级联的支架分子。我们的研究结果表明，Brx通过提高细胞内渗透压和刺激细胞因子的产生来整合免疫细胞对渗透压应激和炎症的反应。
Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macromolecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a transcription factor that induces the expression of hyperosmolarity-responsive genes and stimulates cytokine production. We report that the guanine nucleotide exchange factor (GEF) Brx [also known as protein kinase A–anchoring protein 13 (AKAP13)] is essential for the expression of nfat5 in response to osmotic stress, thus transmitting the extracellular hyperosmolarity signal and enabling differentiation of splenic B cells and production of immunoglobulin. This process required the activity of p38 mitogen-activated protein kinase (MAPK) and NFAT5 and involved a physical interaction between Brx and c-Jun N-terminal kinase (JNK)–interacting protein 4 (JIP4), a scaffold molecule specific to activation of the p38 MAPK cascade. Our results indicate that Brx integrates the responses of immune cells to osmotic stress and inflammation by elevating intracellular osmolarity and stimulating the production of cytokines.
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影响因子：
14.9
作者：
Esensten, JH;Tsytsykova, AV;Lopez-Rodriguez, C;Ligeiro, FA;Rao, A;Goldfeld, AE
通讯作者：
Goldfeld, AE
影响因子：
2.7
作者：
Bai, Xueyan;Wu, Jun;Su, Yan A.
通讯作者：
Su, Yan A.
影响因子：
4.8
作者：
Diviani, D;Soderling, J;Scott, JD
通讯作者：
Scott, JD
影响因子：
4.8
作者：
Hehner, SP;Hofmann, TG;Schmitz, ML
通讯作者：
Schmitz, ML
DOI：
10.1073/pnas.0403139101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Go, WY;Liu, XB;Ho, SN
通讯作者：
Ho, SN