Cell type specificity of PI3K signaling in Pdk1-and Pten-deficient brains
Cell type specificity of PI3K signaling in Pdk1-and Pten-deficient brains
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DOI：
10.1101/gad.1799609
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发表时间：
2009-07-15
影响因子：
10.5
通讯作者：
Baker, Suzanne J.
中科院分区：
文献类型：
--
作者：
Chalhoub, Nader;Zhu, Guo;Baker, Suzanne J.
PTEN 的缺失会导致磷脂酰肌醇 3 激酶 (PI3K) 信号下游成分（包括 PDK1）不受调节的激活，并破坏正常的神经系统发育和体内平衡。我们测试了 Pdk1 对大脑中 Pten 缺失引起的异常的影响。 Pdk1 的条件性缺失导致小头畸形。 Pdk1 和 Pten 的联合删除可以挽救肥大，但不能挽救 Pten 缺陷神经元的迁移缺陷。 Pdk1 失活对神经胶质细胞和神经元中磷酸化 Akt 的调节产生显着不同的影响。我们的结果显示 Pten 缺陷大脑中存在 Pdk1 依赖性和 Pdk1 独立性异常，并证明普遍存在的 PI3K 通路的反馈调节存在细胞类型特异性差异。
Loss of PTEN causes unregulated activation of downstream components of phosphatidylinositol 3-kinase (PI3K) signaling, including PDK1, and disrupts normal nervous system development and homeostasis. We tested the contribution of Pdk1 to the abnormalities induced by Pten deletion in the brain. Conditional deletion of Pdk1 caused microcephaly. Combined deletion of Pdk1 and Pten rescued hypertrophy, but not migration defects of Pten-deficient neurons. Pdk1 inactivation induced strikingly different effects on the regulation of phosphorylated Akt in glia versus neurons. Our results show Pdk1-dependent and Pdk1-independent abnormalities in Pten-deficient brains, and demonstrate cell type specific differences in feedback regulation of the ubiquitous PI3K pathway.