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论文题目: The protein phosphatase activity of PTEN is essential for regulating neural stem cell differentiation
英文论文题目: The protein phosphatase activity of PTEN is essential for regulating neural stem cell differentiation
第一作者: Lyu, JW; Yu, XY; He, LJ; Cheng, TL; Zhou, JJ; Cheng, C; Chen, ZF; Cheng, GQ; Qiu, ZL; Zhou, WH
英文第一作者: Lyu, JW; Yu, XY; He, LJ; Cheng, TL; Zhou, JJ; Cheng, C; Chen, ZF; Cheng, GQ; Qiu, ZL; Zhou, WH
联系作者: Zhou, WH (reprint author), Fudan Univ, Childrens Hosp, Dept Neonatol, 399 Wanyuan Rd, Shanghai 201102, Peoples R China.
英文联系作者: Zhou, WH (reprint author), Fudan Univ, Childrens Hosp, Dept Neonatol, 399 Wanyuan Rd, Shanghai 201102, Peoples R China.
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发表年度: 2015
卷: 8
期:
页码: -
摘要: Background: The tumor suppressor gene Phosphatase and tensin homolog (PTEN) is highly expressed in neural progenitor cells (NPCs) and plays an important role in development of the central nervous system. As a dual-specificity phosphatase, the loss of PTEN phosphatase activity has been linked to various diseases. Results: Here we report that the protein phosphatase activity of Pten is critical for regulating differentiation of neural progenitor cells. First we found that deletion of Pten promotes neuronal differentiation. To determine whether the protein or lipid phosphatase activity is required for regulating neuronal differentiation, we generated phosphatase domain-specific Pten mutations. Interestingly, only expression of protein phosphatase-deficient mutant Y138L could mimic the effect of knocking down Pten, suggesting the protein phosphatase of Pten is critical for regulating NPC differentiation. Importantly, we showed that the wild-type and lipid phosphatase mutant (G129E) forms of Pten are able to rescue neuronal differentiation in Pten knockout NPCs, but mutants containing protein phosphatase mutant cannot. We further found that Pten-dependent dephosphorylation of CREB is critical for neuronal differentiation. Conclusion: Our data indicate that the protein phosphatase activity of PTEN is critical for regulating differentiation of NSCs during cortical development.
英文摘要: Background: The tumor suppressor gene Phosphatase and tensin homolog (PTEN) is highly expressed in neural progenitor cells (NPCs) and plays an important role in development of the central nervous system. As a dual-specificity phosphatase, the loss of PTEN phosphatase activity has been linked to various diseases. Results: Here we report that the protein phosphatase activity of Pten is critical for regulating differentiation of neural progenitor cells. First we found that deletion of Pten promotes neuronal differentiation. To determine whether the protein or lipid phosphatase activity is required for regulating neuronal differentiation, we generated phosphatase domain-specific Pten mutations. Interestingly, only expression of protein phosphatase-deficient mutant Y138L could mimic the effect of knocking down Pten, suggesting the protein phosphatase of Pten is critical for regulating NPC differentiation. Importantly, we showed that the wild-type and lipid phosphatase mutant (G129E) forms of Pten are able to rescue neuronal differentiation in Pten knockout NPCs, but mutants containing protein phosphatase mutant cannot. We further found that Pten-dependent dephosphorylation of CREB is critical for neuronal differentiation. Conclusion: Our data indicate that the protein phosphatase activity of PTEN is critical for regulating differentiation of NSCs during cortical development.
刊物名称: MOLECULAR BRAIN
英文刊物名称: MOLECULAR BRAIN
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学科: Neurosciences & Neurology
英文学科: Neurosciences & Neurology
影响因子: 4.902
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论文类别: Article
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