Allosteric modulation of adenosine A1 and cannabinoid 1 receptor signaling by G-peptides.
Allosteric modulation of adenosine A1 and cannabinoid 1 receptor signaling by G-peptides.
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DOI：
10.1002/prp2.673
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发表时间：
2020-12
影响因子：
2.6
通讯作者：
Sivaramakrishnan S
中科院分区：
文献类型：
--
作者：
Touma AM;Malik RU;Gupte T;Sivaramakrishnan S
While allosteric modulation of GPCR signaling has gained prominence to address the need for receptor specificity, efforts have mainly focused on allosteric sites adjacent to the orthosteric ligand‐binding pocket and lipophilic molecules that target transmembrane helices. In this study, we examined the allosteric influence of native peptides derived from the C‐terminus of the Gα subunit (G‐peptides) on signaling from two Gi‐coupled receptors, adenosine A1 receptor (A1R) and cannabinoid receptor 1 (CB1). We expressed A1R and CB1 fusions with G‐peptides derived from Gαs, Gαi, and Gαq in HEK 293 cells using systematic protein affinity strength modulation (SPASM) and monitored the impact on downstream signaling in the cell compared to a construct lacking G‐peptides. We used agonists N6‐Cyclopentyladenosine (CPA) and 5’‐N‐Ethylcarboxamidoadenosine (NECA) for A1R and 2‐Arachidonoylglycerol (2‐AG) and WIN 55,212‐2 mesylate (WN) for CB1. G‐peptides derived from Gαi and Gαq enhance agonist‐dependent cAMP inhibition, demonstrating their effect as positive allosteric modulators of Gi‐coupled signaling. In contrast, both G‐peptides suppress agonist‐dependent IP1 levels suggesting that they differentially function as negative allosteric modulators of Gq‐coupled signaling. Taken together with our previous studies on Gs‐coupled receptors, this study provides an extended model for the allosteric effects of G‐peptides on GPCR signaling, and highlights their potential as probe molecules to enhance receptor specificity. Gα peptides differentially impact Gs and Gi signaling in Cannabinoid (CB1) receptors.
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DOI：
10.1038/nrd2760
发表时间：
2009-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
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DOI：
10.1073/pnas.1617232114
发表时间：
2017-04-04
影响因子：
11.1
作者：
Gupte, Tejas M.;Malik, Rabia U.;Sivaramakrishnan, Sivaraj
通讯作者：
Sivaramakrishnan, Sivaraj
影响因子：
7.3
作者：
Chen, X. P.;Yang, W.;Zhou, N. M.
通讯作者：
Zhou, N. M.
影响因子：
4.1
作者：
FREISSMUTH, M;SELZER, E;SCHUTZ, W
通讯作者：
SCHUTZ, W
DOI：
10.1126/stke.2002.118.pl1
发表时间：
2002-02-05
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Gilchrist, Annette;Li, Anli;Hamm, Heidi E
通讯作者：
Hamm, Heidi E