内分泌
词汇介绍
拓展阅读
解析
phosphoinositide 英/,fɔsfəui'nəusitaid/
释 义 n. 磷酸肌醇
例 句 The milestone for a central role of lipids in signal transduction was manifested by the discovery of the phosphoinositide cycle.磷酸肌醇循环的发现以里程碑的形式证明了脂质在细胞信号转导过程中发挥重要作用。
kinase 英 /ˈkaɪneɪz/ 美 /ˈkɪnneɪz/
释 义 n. [生化] 激酶；致活酶
例 句 The scientists successfully identified the small enzyme molecule responsible, a gene called focal adhesion kinase.科学家成功分离出这种小小的酶分子，基因学上称之为局部粘着激酶。
概述
概述
磷酸肌醇3-激酶（PI3K），是一类涉及细胞功能的酶，例如细胞生长，增殖，分化，运动，存活和细胞内运输，而这些细胞又参与癌症。PI3K能够使磷脂酰肌醇（PtdIns）的肌醇环的3位羟基磷酸化。该通路与癌基因PIK3CA和肿瘤抑制物PTEN一起，与癌症对胰岛素和IGF1的敏感性以及卡路里限制有关。
分类
①I类PI3K 在体内催化磷脂酰肌醇（4,5）-双磷酸（PI（4,5）P 2）转化为磷脂酰肌醇（3,4,5）-三磷酸（PI（3,4,5）P 3）。在体外时，还显示它们可将磷脂酰肌醇（PI）转化为磷脂酰肌醇3-磷酸酯（PI3P）和磷脂酰肌醇4-磷酸酯（PI4P）转化为磷脂酰肌醇（3,4）-双磷酸酯（PI（3,4）P 2），这些反应在体内非常不利。
②II类PI3K的独特特征是C端C2域。该结构域缺乏关键的Asp残基来协调钙离子的结合，这表明II类PI3Ks以钙离子独立的方式结合脂质。II类包含三种催化同工型（C2α，C2β和C2γ），但与I和III类不同，它没有调节蛋白。II类催化由PI产生的PI（3）P和由PI（4）P产生的PI（3,4）P 2；然而，关于它们在免疫细胞中的作用知之甚少。然而，PI（3,4）P 2已被证明在网格蛋白介导的内吞作用的侵入阶段中起作用。C2α和C2β在体内表达，但C2γ的表达仅限于肝细胞。
③III类PI3K仅从PI产生PI（3）P，但在结构上更类似于I类，因为它们以催化（Vps34）和调节（Vps15 / p150）亚基的异二聚体形式存在。III类似乎主要参与蛋白质和囊泡的运输。然而，有证据表明它们能够促进对免疫细胞重要的几个过程的有效性，尤其是吞噬作用。
④一组与远距离相关的酶有时称为IV类PI3K。它由共济失调毛细血管扩张突变（ATM），共济失调毛细血管扩张和Rad3相关（ATR），DNA依赖性蛋白激酶（DNA-PK）和雷帕霉素的哺乳动物靶标（mTOR）组成。它们是蛋白质丝氨酸/苏氨酸激酶。
功能
PI3K已与一组极为不同的细胞功能相关，包括细胞生长，增殖，分化，运动，存活和细胞内运输。这些功能中的许多功能都与PI3K / AKT / mTOR途径中的 I类PI3K激活蛋白激酶B（PKB，aka Akt）的能力有关。该p110δ和p110γ亚型调节免疫反应的不同方面。PI3Ks也是胰岛素信号通路的关键组成部分。
复制标题棕色脂肪组织中急性b肾上腺素受体介导的葡萄糖清除; 独立于功能性胰岛素Q4信号的独特途径
发表时间：2019-11-01
影响指数：6.2
作者： Jessica M Olsen
期刊：MOL METAB
In this study, while insulin resulted in a pronounced phosphorylation of Akt at both Thr308 and Ser473, isoproterenol did not affect Akt phosphorylation at Thr308 but increased Akt Ser473 phosphorylation. The general consensus is that Akt requires phosphorylation at both Ser473 and Thr308 to be fully active. It has been proposed that phosphorylation at Thr308 alone can partially activate Akt, but phosphorylation solely at Ser473 has not been proposed to have any stimulatory effect. This would then indicate that the weak phosphorylation at Akt Ser473 we observe in brown adipocytes treated with isoproterenol is in itself not enough for activating Akt. In addition, since we observed no phosphorylation of Akt at Thr308, there is no reason to believe that partial activation of Akt has any role in adrenoceptor stimulated glucose uptake. We hypothesized that Akt phosphorylation at Ser473 following isoproterenol treatment could be explained by residual effects due to insufficient insulin starvation prior to the experiment. Generally, to eliminate any effects of insulin signaling in brown adipocytes, the cells are routinely incubated with insulin-free medium 30 min prior to the start of most experiments. We hypothesized that this time frame was too short to completely eliminate effects of the insulin from the preceding medium and could explain the apparent b-adrenoceptor mediated Akt phosphorylation in vitro. It has been shown that mTORC2 activity at the plasma membrane is constitutive and PI3K-insensitive, so that membrane recruitment of Akt is sufficient for it to be phosphorylated at Ser473 by mTORC2. We hypothesized that the badrenoceptor mediated Akt phosphorylation could be explained by recruitment of Akt to the plasma membrane as a consequence of residual insulin in parallel with the recruitment and activation of mTORC2 by isoproterenol treatment. We therefore insulin-starved brown adipocytes for varying lengths of time prior to stimulation with isoproterenol and measured Akt phosphorylation and glucose uptake. Isoproterenol treatment had no effect on Akt Ser473 phosphorylation when the cells had been insulin starved for 24 h. However, in these cells, isoproterenol was fully able to induce glucose uptake thereby signifying that the phosphorylation of Akt is inconsequential to the effects of b-adrenoreceptor mediated induction of glucose uptake in brown adipocytes.
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