Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, PR China.
FEBS Lett. 2010 Jun 3;584(11):2207-12. doi: 10.1016/j.febslet.2010.03.039. Epub 2010 Mar 29.
The beta-2 adrenergic receptor (beta2AR) has a carboxyl terminus motif that can interact with PSD-95/discs-large/ZO1 homology (PDZ) domain-containing proteins. In this paper, we identified membrane-associated guanylate kinase inverted-3 (MAGI-3) as a novel binding partner of beta2AR. The carboxyl terminus of beta2AR binds with high affinity to the fifth PDZ domain of MAGI-3, with the last four amino acids (D-S-L-L) of the receptor being the key determinants of the interaction. In cells, the association of full-length beta2AR with MAGI-3 occurs constitutively and is enhanced by agonist stimulation of the receptor. Our data also demonstrated that beta2AR-stimulated extracellular signal-regulated kinase-1/2 (ERK1/2) activation was substantially retarded by MAGI-3 expression. These data suggest that MAGI-3 regulates beta2AR-mediated ERK activation through the physical interaction between beta2AR and MAGI-3.
β2 肾上腺素能受体 (β2AR) 的羧基末端基序可与 PSD-95/ 离散大/ZO1 同源 (PDZ) 域蛋白相互作用。在本文中，我们鉴定了膜相关鸟苷酸激酶倒置 3 (MAGI-3) 为β2AR 的一个新的结合伴侣。β2AR 的羧基末端与 MAGI-3 的第五个 PDZ 结构域具有高亲和力，受体的最后四个氨基酸 (D-S-L-L) 是相互作用的关键决定因素。在细胞中，全长β2AR 与 MAGI-3 的结合是组成性的，并且受受体激动剂的刺激增强。我们的数据还表明，MAGI-3 表达显著延缓了β2AR 刺激的细胞外信号调节激酶 1/2 (ERK1/2) 的激活。这些数据表明，MAGI-3 通过β2AR 和 MAGI-3 之间的物理相互作用调节β2AR 介导的 ERK 激活。
