The anti-apoptotic response of the Gq/11-coupled muscarinic receptor family.
The anti-apoptotic response of the Gq/11-coupled muscarinic receptor family.
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DOI：
10.1042/bst0311182
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发表时间：
2003-12
影响因子：
3.9
通讯作者：
A. Tobin;D. Budd
中科院分区：
文献类型：
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作者：
A. Tobin;D. Budd
现在很清楚，g蛋白偶联受体可以通过多种依赖于细胞类型和受体亚型的机制调节程序性细胞死亡（凋亡）。在这里，我们提出证据表明，毒蕈碱受体家族的G（q/11）偶联亚型(即M(1)， M（3)和M(5)-毒蕈碱受体亚型）能够防止凋亡细胞死亡。特别是，我们证明M(3)-毒蕈碱受体的c端尾部是抗凋亡信号通路的重要结构元件。去除C末端尾部的远端部分导致受体正常偶联G(q/11)/磷脂酶C途径和有丝分裂原激活的蛋白激酶途径，但不能偶联抗凋亡途径。此外，G（q/11）偶联毒蕈碱受体亚型的c端尾部保守的多碱基区域似乎是偶联抗凋亡途径的结构决定因素。
It is now clear that G-protein-coupled receptors can regulate programmed cell death (apoptosis) through a variety of mechanisms that are dependent on cell type and receptor subtype. Here we present evidence that the G(q/11)-coupled subtypes of the muscarinic receptor family (namely M(1), M(3) and M(5)-muscarinic receptor subtypes) are able to protect against apoptotic cell death. In particular we demonstrate that the C-terminal tail of the M(3)-muscarinic receptor is an essential structural element for signalling to the anti-apoptotic pathway. Removal of the distal portion of the C-terminal tail results in a receptor that is coupled normally to the G(q/11)/phospholipase C pathway and the mitogen-activated protein kinase pathway, but is unable to couple to the anti-apoptotic pathway. Furthermore, a poly-basic region conserved within the C-terminal tail of the G(q/11)-coupled muscarinic receptor subtypes appears to be the structural determinant of coupling to the anti-apoptotic pathway.