Constitutive activation of chimeric m2/m5 muscarinic receptors and delineation of G-protein coupling selectivity domains.
Constitutive activation of chimeric m2/m5 muscarinic receptors and delineation of G-protein coupling selectivity domains.
复制标题
嵌合 m2/m5 毒蕈碱受体的组成型激活和 G 蛋白偶联选择性结构域的描绘。
DOI：
10.1016/0006-2952(95)02234-1
复制
发表时间：
1996
影响因子：
5.8
通讯作者：
Brann,MR
中科院分区：
文献类型：
--
作者：
Burstein,ES;Spalding,TA;Brann,MR
为了获得毒蕈碱受体/G蛋白偶联的结构/功能关系，在细胞增殖/转化测定中测试m2和m5毒蕈碱受体和一系列m2 m5嵌合体的激动剂结合和功能反应。介导磷脂酰肌醇周转刺激的M5在增殖测定中显示出强活性，而介导腺苷酸环化酶抑制的M2在增殖测定中无活性。在i2或i3环中含有m2序列的嵌合体分别具有受损的活性或无活性。含有从N-末端到TM 2或从TM 6到C-末端的M2片段的嵌合体相对于M5具有增强的活性，并且具有这两个元件的嵌合体被组成性激活。
To derive structure/function relationships for muscarinic receptor/G-protein coupling, the m2 and m5 muscarinic receptors and a series of m2 m5 chimeras were tested for agonist binding and functional responses in a cellular proliferation/transformation assay. m5, which mediates stimulation of phosphatidylinositol turnover, displayed robust activity in the proliferation assay, whereas m2, which mediates inhibition of adenylyl cyclase, was inactive in the proliferation assay. Chimeras that contained m2 sequences in the i2 or i3 loops had impaired activity or were inactive, respectively. Chimeras that contained m2 segments reaching from the N-terminus to TM2, or from TM6 to the C-terminus, had enhanced activity relative to m5, and a chimera with both of these elements was constitutively activated.