Phosphorylation and regulation of a G protein-coupled receptor by protein kinase CK2.
Phosphorylation and regulation of a G protein-coupled receptor by protein kinase CK2.
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DOI：
10.1083/jcb.200610018
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发表时间：
2007-04-09
期刊：
影响因子：
--
通讯作者：
Tobin AB
中科院分区：
文献类型：
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作者：
Torrecilla I;Spragg EJ;Poulin B;McWilliams PJ;Mistry SC;Blaukat A;Tobin AB
我们证明了蛋白激酶酪蛋白激酶 2 (CK2) 在转染细胞和小脑颗粒神经元中 M3 毒蕈碱受体的磷酸化和调节中的作用。在激动剂占据时，受体磷酸受体位点的特定子集（包括第三个细胞内环中的 SASSDEED 基序）被 CK2 磷酸化。 CK2 介导的受体磷酸化特异性调节受体与 Jun 激酶途径的偶联。重要的是，其他磷酸化依赖性受体过程受不同于 CK2 的激酶调节。我们得出的结论是，G 蛋白偶联受体 (GPCR) 可以通过来自多种激酶家族的蛋白激酶以激动剂依赖性方式磷酸化，而不仅仅是 GPCR 激酶，并且特定激酶的受体磷酸化决定特定的信号转导结果。此外，我们证明M3-毒蕈碱受体在不同的细胞类型中可以被差异性地磷酸化，这表明磷酸化是一种灵活的调节过程，其中被磷酸化的位点以及因此的信号转导结果取决于表达受体的细胞类型。
We demonstrate a role for protein kinase casein kinase 2 (CK2) in the phosphorylation and regulation of the M3-muscarinic receptor in transfected cells and cerebellar granule neurons. On agonist occupation, specific subsets of receptor phosphoacceptor sites (which include the SASSDEED motif in the third intracellular loop) are phosphorylated by CK2. Receptor phosphorylation mediated by CK2 specifically regulates receptor coupling to the Jun-kinase pathway. Importantly, other phosphorylation-dependent receptor processes are regulated by kinases distinct from CK2. We conclude that G protein–coupled receptors (GPCRs) can be phosphorylated in an agonist-dependent fashion by protein kinases from a diverse range of kinase families, not just the GPCR kinases, and that receptor phosphorylation by a defined kinase determines a specific signalling outcome. Furthermore, we demonstrate that the M3-muscarinic receptor can be differentially phosphorylated in different cell types, indicating that phosphorylation is a flexible regulatory process where the sites that are phosphorylated, and hence the signalling outcome, are dependent on the cell type in which the receptor is expressed.