Inositol pyrophosphates as mammalian cell signals.
Inositol pyrophosphates as mammalian cell signals.
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DOI：
10.1126/scisignal.2001958
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发表时间：
2011-08-23
影响因子：
7.3
通讯作者：
Snyder SH
中科院分区：
文献类型：
--
作者：
Chakraborty A;Kim S;Snyder SH
肌醇焦磷酸盐是高能肌醇多磷酸分子，存在于从粘菌、酵母到哺乳动物的生物体中。不同类别的酶产生不同形式的肌醇焦磷酸。这些物质的生物合成主要涉及肌醇六磷酸（IP6）的磷酸化以生成焦磷酸IP7。对这些物质功能的初步了解主要来自酵母，其中含有 IP6 激酶 (yIP6K) 的单一亚型，以及粘菌盘基网柄菌。通过使用细胞系来研究肌醇焦磷酸的哺乳动物功能，以确定其在各种过程中的作用，包括胰岛素分泌和细胞凋亡。最近，靶向删除 IP6K 同工型以及相关肌醇多磷酸多激酶 (IPMK) 的小鼠大大增强了我们对肌醇多磷酸生理学的理解。缺乏肌醇六磷酸激酶 1 (IP6K1) 的小鼠的表型改变揭示了这些分子在胰岛素稳态、肥胖和免疫功能中的信号传导作用。肌醇焦磷酸至少部分通过抑制丝氨酸-苏氨酸激酶 Akt 的激活来调节这些过程。对 IP6K2 的类似研究表明，这种酶是一种细胞死亡诱导剂，通过刺激促凋亡蛋白 p53 发挥作用。 IPMK 负责生成肌醇磷酸 IP5，但也具有磷脂酰肌醇 3-激酶活性，参与 Akt 的激活。在这里，我们讨论了了解肌醇焦磷酸生理功能的最新进展，这在很大程度上基于对 IP6K 同种型缺失的小鼠的研究。这些发现强调了 IPMK 和 IP6K 在调节生长因子和营养介导的细胞信号传导中的相互作用。
Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphosphate (IP6) to generate the pyrophosphate IP7. Initial insights into functions of these substances derived primarily from yeast, which contain a single isoform of IP6 kinase (yIP6K), as well as from the slime mold Dictyostelium. Mammalian functions for inositol pyrophosphates have been investigated by using cell lines to establish roles in various processes, including insulin secretion and apoptosis. More recently, mice with targeted deletion of IP6K isoforms as well as the related inositol polyphosphate multikinase (IPMK) have substantially enhanced our understanding of inositol polyphosphate physiology. Phenotypic alterations in mice lacking inositol hexakisphosphate kinase 1 (IP6K1) reveal signaling roles for these molecules in insulin homeostasis, obesity, and immunological functions. Inositol pyrophosphates regulate these processes at least in part by inhibiting activation of the serine-threonine kinase Akt. Similar studies of IP6K2 establish this enzyme as a cell death inducer acting by stimulating the proapoptotic protein p53. IPMK is responsible for generating the inositol phosphate IP5 but also has phosphatidylinositol 3-kinase activity—that participates in activation of Akt. Here, we discuss recent advances in understanding the physiological functions of the inositol pyrophosphates based in substantial part on studies in mice with deletion of IP6K isoforms. These findings highlight the interplay of IPMK and IP6K in regulating growth factor and nutrient-mediated cell signaling.
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影响因子：
64.5
作者：
Chakraborty A;Koldobskiy MA;Bello NT;Maxwell M;Potter JJ;Juluri KR;Maag D;Kim S;Huang AS;Dailey MJ;Saleh M;Snowman AM;Moran TH;Mezey E;Snyder SH
通讯作者：
Snyder SH
影响因子：
3.6
作者：
Choi, Kuicheon;Mollapour, Elahe;Shears, Stephen B.
通讯作者：
Shears, Stephen B.
影响因子：
30.8
作者：
Emamian, ES;Hall, D;Gogos, JA
通讯作者：
Gogos, JA
DOI：
10.1073/pnas.0909176106
发表时间：
2009-12-15
影响因子：
11.1
作者：
Azevedo, Cristina;Burton, Adam;Saiardi, Adolfo
通讯作者：
Saiardi, Adolfo
影响因子：
4.8
作者：
Choi, Jae H.;Williams, Jason;Shears, Stephen B.
通讯作者：
Shears, Stephen B.