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您的检索式：作者名="Adam S.Lazorchak"
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| 1 | Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc显示文摘Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism. | Man Li Adam S.Lazorchak Xinxing Ouyang Huihui Zhang Hongzhi Liu Omotooke A.Arojo Lichong Yan Jingsi Jin Yuheng Han Guojun Qu Yuhong Fu Xiaocao Xu Xiaobo Liu Wenqian Zhang Zhengfeng Yang Chuan Ruan Qijun Wang Dou Liu Chuanxin Huang Lu Lu Shibo Jiang Fubin Li Bing Su | 2019 | Cellular & Molecular Immunology2019，16，9： | 4 |
| 2 | Perspectives on the role of mTORC2 in B lymphocyte development,immunity and tumorigenesis显示文摘Mammalian target of rapamycin complex 2(mTORC2)is a key downstream mediator of phosphoinositol-3-kinase(PI3K)dependent growth factor signaling.In lymphocytes,mTORC2 has emerged as an important regulator of cell development,homeostasis and immune responses.However,our current understanding of mTORC2 functions and the molecular mechanisms regulating mTORC2 signaling in B and T cells are still largely incomplete.Recent studies have begun to shed light on this important pathway.We have previously reported that mTORC2 mediates growth factor dependent phosphorylation of Akt and facilitates Akt dependent phosphorylation and inactivation of transcription factors FoxO1 and FoxO3a.We have recently explored the functions of mTORC2 in B cells and show that mTORC2 plays a key role in regulating survival and immunoglobulin(Ig)gene recombination of bone marrow B cells through an Akt2-FoxO1 dependent mechanism.Ig recombination is suppressed in proliferating B cells to ensure that DNA double strand breaks are not generated in actively dividing cells.Our results raise the possibility that genetic or pharmacologic inhibition of mTORC2 may promote B cell tumor development as a result of inefficient suppression of Ig recombination in dividing B cells.We also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability. | Adam S.Lazorchak Bing Su | 2011 | Protein & Cell2011，2，7： | 2 |
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