Fujii Seiji, Yamazoe Ginko, Itoh Masayuki, Kubo Yoshihiro, Saitoh Osamu
Department of Bio-Science, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama-shi, Shiga, Japan.
Biochem Biophys Res Commun. 2008 Dec 5;377(1):200-4. doi: 10.1016/j.bbrc.2008.09.096. Epub 2008 Oct 1.
We showed previously that RGS8 directly binds to the third intracellular loop (i3L) of the M1 muscarinic acetylcholine receptor using the sequence MPRR at the N-terminus of RGS8 and specifically inhibits signal transduction. Here, we identified spinophilin (SPL) as an RGS8-interacting protein. We found that the SPL-binding site of RGS8 is the MPRR sequence, and the M1 receptor and SPL compete for binding to RGS8. However, we also observed that the expression of SPL significantly enhances the inhibitory function of RGS8, and that SPL can bind to the M1 receptor, demonstrating the indirect binding of RGS8 to the M1 receptor through SPL for an efficient regulatory function.
我们之前表明，RGS8利用其N端的MPRR序列直接结合M1毒蕈碱型乙酰胆碱受体的第三个细胞内环（i3L），并特异性抑制信号转导。在此，我们鉴定出亲嗜素（SPL）是一种与RGS8相互作用的蛋白。我们发现RGS8的SPL结合位点是MPRR序列，且M1受体与SPL竞争结合RGS8。然而，我们还观察到SPL的表达显著增强了RGS8的抑制功能，并且SPL可结合M1受体，这表明RGS8通过SPL间接结合M1受体以实现有效的调节功能。
