Parry Richard V, Harris Stephanie J, Ward Stephen G
Inflammatory Cell Biology Laboratory, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
Biochim Biophys Acta. 2010 Mar;1804(3):592-7. doi: 10.1016/j.bbapap.2009.09.019. Epub 2009 Sep 25.
The phosphoinositide 3-kinase signaling pathway regulates a range of T lymphocyte cellular functions including growth, proliferation, cytokine secretion and survival. Aberrant regulation of phosphoinositide 3-kinase-dependent signaling in T lymphocytes has been implicated in inflammatory and autoimmune diseases. In common with much of the immune system, several mechanisms exist to ensure the pathway is tightly regulated to elicit appropriate responses. One level of control involves the Src homology 2 domain-containing inositol-5-phosphatase-1 (SHIP-1) that modulates phosphoinositide 3-kinase signaling by degrading the key signaling lipid PI(3,4,5)P(3) to PI(3,4)P(2), but also serves as a key scaffolding molecule in the formation of multi-protein complexes. Here we discuss the role of SHIP-1 in regulating T lymphocyte and immune function, as well as its potential as a therapeutic target.
磷脂酰肌醇3-激酶信号通路调节一系列T淋巴细胞的细胞功能，包括生长、增殖、细胞因子分泌和存活。T淋巴细胞中磷脂酰肌醇3-激酶依赖性信号的异常调节与炎症和自身免疫性疾病有关。与免疫系统的许多部分一样，存在多种机制来确保该信号通路受到严格调控以引发适当的反应。其中一种控制水平涉及含Src同源2结构域的肌醇-5-磷酸酶-1（SHIP-1），它通过将关键信号脂质PI(3,4,5)P(3)降解为PI(3,4)P(2)来调节磷脂酰肌醇3-激酶信号，而且在多蛋白复合物的形成中作为关键的支架分子。在此，我们讨论SHIP-1在调节T淋巴细胞和免疫功能中的作用，以及其作为治疗靶点的潜力。
