Role of inositol poly-phosphatases and their targets in T cell biology.
Role of inositol poly-phosphatases and their targets in T cell biology.
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DOI：
10.3389/fimmu.2013.00288
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发表时间：
2013-09-23
影响因子：
7.3
通讯作者：
Kerr WG
中科院分区：
文献类型：
--
作者：
Srivastava N;Sudan R;Kerr WG
T淋巴细胞在包括粘膜表面在内的所有解剖部位的宿主防御中起关键作用。这不仅包括免疫系统的效应臂，还包括免疫应答的调节以防止自身免疫。PI 3 K同种型的遗传靶向表明通过PI 3 K产生PI（3，4，5）P3在促进效应T细胞应答中起关键作用。因此，能够靶向PI（3，4，5）P3的5′-和3′-肌醇多磷酸酶SHIP 1、SHIP 2以及磷酸酶和张力蛋白同源物是体内T细胞效应子功能的潜在遗传决定因素。此外，5′-肌醇多磷酸酶SHIP 1和2可以将PI（3，4，5）P3分流到罕见但有效的信号传导磷酸肌醇种类PI（3，4）P2，因此这些SHIP 1/2和消耗PI（3，4）P2的INPP 4 A/B酶可能在T细胞生物学中具有精确的作用，以放大或抑制选择性募集到PI（3，4）P2并被PI（3，4）P2激活的PI 3 K信号传导效应物。在这里，我们总结了最近的遗传和化学证据，表明肌醇多磷酸酶在T细胞区室的效应器和调节功能中具有重要作用。此外，我们将讨论未来可能进行的遗传学研究，以进一步阐述这些酶在T细胞生物学中的作用，以及这些酶在疾病环境中用于治疗目的的潜在药物操作，其中T细胞功能是体内关键靶点。
T lymphocytes play a critical role in host defense in all anatomical sites including mucosal surfaces. This not only includes the effector arm of the immune system, but also regulation of immune responses in order to prevent autoimmunity. Genetic targeting of PI3K isoforms suggests that generation of PI(3,4,5)P3 by PI3K plays a critical role in promoting effector T cell responses. Consequently, the 5′- and 3′-inositol poly-phosphatases SHIP1, SHIP2, and phosphatase and tensin homolog capable of targeting PI(3,4,5)P3 are potential genetic determinants of T cell effector functions in vivo. In addition, the 5′-inositol poly-phosphatases SHIP1 and 2 can shunt PI(3,4,5)P3 to the rare but potent signaling phosphoinositide species PI(3,4)P2 and thus these SHIP1/2, and the INPP4A/B enzymes that deplete PI(3,4)P2 may have precise roles in T cell biology to amplify or inhibit effectors of PI3K signaling that are selectively recruited to and activated by PI(3,4)P2. Here we summarize recent genetic and chemical evidence that indicates the inositol poly-phosphatases have important roles in both the effector and regulatory functions of the T cell compartment. In addition, we will discuss future genetic studies that might be undertaken to further elaborate the role of these enzymes in T cell biology as well as potential pharmaceutical manipulation of these enzymes for therapeutic purposes in disease settings where T cell function is a key in vivo target.
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影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
56.9
作者：
Franke, TF;Kaplan, DR;Toker, A
通讯作者：
Toker, A
影响因子：
4.4
作者：
Brooks, Robert;Fuhler, Gwenny M.;Kerr, William G.
通讯作者：
Kerr, William G.
影响因子：
5.4
作者：
Collazo, Michelle M.;Paraiso, Kim H. T.;Park, Mi-Young;Hazen, Amy L.;Kerr, William G.
通讯作者：
Kerr, William G.
影响因子：
56.9
作者：
Di Cristofano, A;Kotsi, P;Pandolfi, PP
通讯作者：
Pandolfi, PP