Redundant expression but selective utilization of nuclear factor of activated T cells family members.
Redundant expression but selective utilization of nuclear factor of activated T cells family members.
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DOI：
10.4049/jimmunol.159.6.2735
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发表时间：
1997-09
影响因子：
4.4
通讯作者：
L. Timmerman;J. I. Healy;S. Ho;L. Chen;C. Goodnow;G. Crabtree
中科院分区：
文献类型：
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作者：
L. Timmerman;J. I. Healy;S. Ho;L. Chen;C. Goodnow;G. Crabtree
活化T细胞核因子（NF-AT）复合物调节许多早期T细胞活化分子的诱导。四个相关蛋白可以作为NF-AT的胞质亚基，它们的重叠表达模式和NF-AT p敲除小鼠的温和表型表明它们可能是功能冗余的。我们表征了成熟淋巴细胞中胞质NF-AT蛋白的分布和活化，并发现NF-AT c、NF-AT p和NF-AT 4/x/c3在成熟T和B细胞中共表达和共调节。每种蛋白质形成独立的DNA结合复合物，并且在生理浓度下，NF-ATc和NF-ATp复合物在占据来自IL-2、IL-3/粒细胞-巨噬细胞CSF、IL-4和CD 40配体基因的NF-AT位点方面胜过NF-AT 4/x/c3。这预测了NF-ATp和NF-ATc的严重冗余的免疫调节功能，但NF-AT 4/x/c3的活性不同。此外，Ab与NF-AT β的相互作用诱导高亲和力的NF-kappaB位点相互作用，表明核伴侣可能显著改变NF-AT家族的特异性。
Nuclear factor of activated T cells (NF-AT) complexes regulate the induction of many early T cell activation molecules. Four related proteins can function as the cytoplasmic subunit of NF-AT, and their overlapping expression patterns and the mild phenotype of the NF-ATp null mice suggest that they may be functionally redundant. We characterized the distribution and activation of cytoplasmic NF-AT proteins in mature lymphocytes and found that NF-ATc, NF-ATp, and NF-AT4/x/c3 are co-expressed and co-regulated in mature T and B cells. Each protein forms independent DNA binding complexes, and at physiologic concentrations, NF-ATc and NF-ATp complexes out-compete NF-AT4/x/c3 for occupancy of NF-AT sites from the IL-2, IL-3/granulocyte-macrophage CSF, IL-4, and CD40 ligand genes. This predicts heavily redundant immune regulatory functions of NF-ATp and NF-ATc, but distinct activities for NF-AT4/x/c3. Additionally, Ab interaction with NF-ATp induces high affinity NF-kappaB site interaction, suggesting that nuclear partners may dramatically vary the specificity of the NF-AT family.