The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development
The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development
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DOI：
10.1038/ni1062
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发表时间：
2004-05-01
影响因子：
30.5
通讯作者：
Cantrell, DA
中科院分区：
文献类型：
--
作者：
Hinton, HJ;Alessi, DR;Cantrell, DA
T 淋巴细胞激活与多种 AGC 丝氨酸激酶（以家族成员蛋白激酶 A、蛋白激酶 G 和蛋白激酶 C 命名）的激活相关。使用简单的基因删除策略很难评估这些分子在 T 细胞发育中的功能，因为不同的 AGC 激酶亚型在胸腺中共表达，并且具有重叠、冗余的功能。为了规避这些问题，我们探索了磷酸肌醇依赖性激酶 1 (PDK1) 基因操作的后果，PDK1 是 AGC 激酶的限速“上游”激活剂。在这里，我们分析了PDK1缺失对T谱系发育的影响。我们还评估了将 PDK1 水平降低至正常值 10% 的后果。 PDK1 完全缺失会阻碍胸腺中的 T 细胞分化，而 PDK1 表达减少则允许 T 细胞分化，但会阻碍增殖扩张。这些研究表明 AGC 家族激酶对于 T 细胞发育至关重要。
T lymphocyte activation is associated with activation of diverse AGC serine kinases (named after family members protein kinase A, protein kinase G and protein kinase C). It has been difficult to assess the function of these molecules in T cell development with simple gene-deletion strategies because different isoforms of AGC kinases are coexpressed in the thymus and have overlapping, redundant functions. To circumvent these problems, we explored the consequences of genetic manipulation of phosphoinositide-dependent kinase 1 (PDK1), a rate-limiting 'upstream' activator of AGC kinases. Here we analyzed the effect of PDK1 deletion on T lineage development. We also assessed the consequences of reducing PDK1 levels to 10% of normal. Complete PDK1 loss blocked T cell differentiation in the thymus, whereas reduced PDK1 expression allowed T cell differentiation but blocked proliferative expansion. These studies show that AGC family kinases are essential for T cell development.