Kinase suppressor of Ras 1 is required for full ERK activation in thymocytes but not for thymocyte selection.
Kinase suppressor of Ras 1 is required for full ERK activation in thymocytes but not for thymocyte selection.
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DOI：
10.1002/eji.201040349
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发表时间：
2010-11
影响因子：
5.4
通讯作者：
Shaw, Andrey S.
中科院分区：
文献类型：
--
作者：
Filbert, Erin L.;Nguyen, AnhCo;Markiewicz, Mary A.;Fowlkes, B. J.;Huang, Yina H.;Shaw, Andrey S.
Ras 1（KSR 1）的支架蛋白激酶抑制因子对于许多细胞类型中ERK的有效激活至关重要。与此相一致，我们观察到缺乏KSR 1的胸腺细胞中ERK激活的缺陷。有趣的是，我们发现PMA刺激后的缺陷比CD 3激活后的缺陷大得多。由于ERK激活被认为对胸腺细胞发育很重要，我们分析了KSR 1缺陷（KSR 1 −/−）小鼠的胸腺细胞选择。我们发现，在两种不同的TCR转基因模型，HY和AND，正选择是正常的。另一方面，HY模型中的阴性选择在KSR 1 −/−小鼠中轻微受损。然而，负选择的缺陷在AND TCR模型系统或内源性超抗原介导的负选择模型中并不明显。这些结果表明，尽管在胸腺细胞中需要KSR 1来完全激活ERK，但是对于大多数胸腺细胞选择事件，完全和有效的ERK激活不是必需的。
The scaffold protein kinase suppressor of Ras 1 (KSR1) is critical for efficient activation of ERK in a number of cell types. Consistent with this, we observed a defect in ERK activation in thymocytes that lack KSR1. Interestingly, we found that the defect was much greater after PMA stimulation than by CD3 activation. Since ERK activation is thought to be important for thymocyte development, we analyzed thymocyte selection in KSR1-deficient (KSR1−/−) mice. We found that positive selection in two different TCR transgenic models, HY and AND, was normal. On the other hand, negative selection in the HY model was slightly impaired in KSR1−/− mice. However, a defect in negative selection was not apparent in the AND TCR model system or in an endogenous superantigen-mediated model of negative selection. These results suggest that, despite a requirement for KSR1 for full ERK activation in thymocytes, full and efficient ERK activation is not essential for the majority of thymocyte selection events.
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