G-ALPHA(15) AND G-ALPHA(16) COUPLE A WIDE VARIETY OF RECEPTORS TO PHOSPHOLIPASE-C
G-ALPHA(15) AND G-ALPHA(16) COUPLE A WIDE VARIETY OF RECEPTORS TO PHOSPHOLIPASE-C
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DOI：
10.1074/jbc.270.25.15175
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发表时间：
1995-06-23
影响因子：
4.8
通讯作者：
SIMON, MI
中科院分区：
文献类型：
--
作者：
OFFERMANNS, S;SIMON, MI
鼠G蛋白α亚基G α（15）及其人对应物G α（16）在造血细胞亚群中表达，并且已显示它们调节肌醇特异性磷脂酶C的β亚型。我们通过在COS-7细胞中连接受体和G蛋白α亚基，研究了多种受体与G α（15）和G α（16）相互作用的能力。在单独表达受体或与G α（q）、G α（11）或G α（14）一起表达受体的细胞中，β（2）肾上腺素能和毒蕈碱M（2）受体的激活导致内源性磷脂酶C的非常小的刺激。然而，当受体与G α（15）和G α（16）共表达时，加入适当的配体导致磷酸肌醇产量增加数倍，这是时间和剂量依赖性的。当先前显示与G（i）和G（s）家族成员偶联的几种其他受体与G α共表达时，观察到磷脂酶C的类似活化（15/16）。此外，通过与磷脂酶C天然偶联的受体刺激磷酸肌醇形成，通过G α（15）和G α（16）的共转染得到增强。这些数据表明，G α（15）和G α（16）是独特的，因为它们可以被多种G蛋白偶联受体激活。G α（15）和G α（16）绕过受体G蛋白相互作用的选择性的能力可能是理解受体诱导的G蛋白激活机制的有用工具。此外，G α（15）和G α（16）对受体的混杂行为可能有助于发现与孤儿受体对应的配体，其信号传导特性未知。
The murine G-protein alpha-subunit G alpha(15) and its human counterpart G alpha(16) are expressed in a subset of hematopoietic cells, and they have been shown to regulate beta-isoforms of inositide-specific phospholipase C. We studied the ability of a variety of receptors to interact with G alpha(15) and G alpha(16) by cotransfecting receptors and G-protein alpha-subunits in COS-7 cells. Activation of beta(2) adrenergic and muscarinic M(2) receptors in cells expressing the receptors alone or together with G alpha(q), G alpha(11), or G alpha(14) led to a very small stimulation of endogenous phospholipase C. However, when the receptors were coexpressed with G alpha(15) and G alpha(16), addition of appropriate ligands caused a severalfold increase in inositol phosphate production which was time- and dose-dependent. A similar activation of phospholipase C was observed when several other receptors which were previously shown to couple to members of the G(i) and G(s) family were coexpressed with G alpha(15/16). In addition, stimulation of inositol phosphate formation via receptors naturally coupled to phospholipase C was enhanced by cotransfection of G alpha(15) and G alpha(16). These data demonstrate that G alpha(15) and G alpha(16) are unique in that they can be activated by a wide variety of G-protein-coupled receptors. The ability of G alpha(15) and G alpha(16) to bypass the selectivity of receptor G-protein interaction can be a useful tool to understand the mechanism of receptor-induced G-protein activation. In addition, the promiscuous behavior of G alpha(15) and G alpha(16) toward receptors may be helpful in finding ligands corresponding to orphan receptors whose signaling properties are unknown.