2020年7月2日 · In this study, we found that megakaryocyte/platelet-specific AGK-deficient mice developed thrombocytopenia and splenomegaly, mainly caused by inefficient bone marrow thrombocytopoiesis and excessive extramedullary hematopoiesis, but not by apoptosis of circulating platelets.

2017年8月3日 · Stable tetracycline-inducible cell lines expressing wild-type and untagged AGK (AGK KO+WT) or FLAG-tagged AGK kinase-dead mutant (AGK G126E) (Bektas et al., 2005) were generated. AGK G126E allowed us to dissect whether AGK function at TIM22 is dependent on the protein’s kinase activity.

2022年4月4日 · AGK deficiency led to severe liver damage and lipid accumulation in mice. Aged mice lacking hepatocyte AGK spontaneously developed NASH. AGK G126E mutation did not affect the structure and function of hepatocytes. AGK deficiency, but not AGK G126E mice, aggravated CDAHFD- and MCD-induced NASH symptoms.

2019年8月6日 · To confirm the role of AGK kinase activity in CD8 + T cell antitumor function, we challenged WT and Agk G126E/G126E mice with highly immunogenic MC38 tumor cells. Agk G126E/G126E mice showed premature lethality ( Figure S7 E), coupled with decreased frequency and number of tumor-infiltrating CD8 + effector T cells but not CD4 + effector T cells ...

2022年4月4日 · Results: The levels of AGK were significantly downregulated in human NASH liver samples. AGK deficiency led to severe liver damage and lipid accumulation in mice. Aged mice lacking hepatocyte AGK spontaneously developed NASH. AGK G126E mutation did not affect the structure and function of hepatocytes.

AGK G126E and JAK2 V617F mutant plasmid were constructed by using the QuikChange Site-Directed Mutagenesis Kit (Stratagene). Endogenous platelet survival was measured after tail intravenous injection of Sulfo-NHS-LC-Biotin (Pierce).

2022年4月4日 · 方法：肝脏特异性 AGK 缺陷小鼠和 AGK G126E 突变（AGK 激酶活性停滞）小鼠采用胆碱缺乏和高脂饮食（CDAHFD）和蛋氨酸胆碱缺乏饮食（MCD）。 研究了 NASH 发病机制中的线粒体功能和 AGK 的分子机制。 结果：人 NASH 肝脏样本中 AGK 的水平显着下调。 AGK 缺乏导致小鼠严重的肝损伤和脂质积累。 缺乏肝细胞 AGK 的老年小鼠自发发展为 NASH。 AGK G126E突变不影响肝细胞的结构和功能。 AGK 缺乏症，但不是 AGK G126E 小鼠，加重了 …

2017年10月1日 · It has been reported that the G126E mutation arrests the kinase activity of AGK. The AGK G126E mutation did not affect peripheral platelet counts or megakaryocyte differentiation, suggesting that the involvement of AGK in megakaryocyte development and platelet biogenesis was not dependent on its kinase activity.

研究人员发现AGK G126E突变不影响外周血血小板计数或巨核细胞分化，表明AGK参与巨核细胞发育和血小板生物发生并不依赖于其激酶活性。 Mpl/JAK2/Stat3通路是调节巨核细胞发育的主要信号通路。 本研究证实，AGK可以与巨核细胞/血小板中的JAK2结合。 此外，研究人员发现JAK2 V617F突变显着增强了AGK与JAK2的结合，并极大地促进了巨核细胞/血小板对血小板生成素刺激时的JAK2/Stat3信号传导。 研究人员还发现JAK2 JH2结构域肽YGVCF617CGDENI序列能增 …

2017年8月3日 · To examine the functional role of the lipid kinase activity of AGK, we introduced a point mutation, which was found to abolish lipid phosphorylation by AGK (Bektas et al., 2005), in the conserved GDG sequence in the glycine-rich loop of its ATP-binding region (G126E). AGK or AGK G126E were expressed in AGK −/− cells under the control of a ...