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Uncovering kappa-opioid receptor agonist-induced PAK1/2 phosphorylation by quantitative phosphoproteomics

Author:
Wu, Jianhong, Jiang, Qinghui, Zhu, Hongwen, Zhou, Yanting, Lu, Dayun, Liu, Xing, Chen, Xiangling, Chen, Jie, Wang, Yujun, Liu, Jinggen, Song, Rentao, Huang, Ruimin, Zhou, Hu
Source:
Biochemical and biophysical research communications 2019 v.516 no.1 pp. 320-326
ISSN:
0006-291X
Subject:
G-protein coupled receptors, actin, agonists, cognition, cytoskeleton, diuresis, immune system, ligands, neurons, nociception, phosphorylation, phosphotransferases (kinases), prediction, proteomics, signal transduction, therapeutics
Abstract:
Kappa-opioid receptor (KOR) is a member of G-protein coupled receptors (GPCRs) expressed in serotonergic neurons and neuronal terminals. The involvement of KOR ligands in nociception, diuresis, emotion, cognition, and immune system has been extensively studied. Omics-based methods are preferable to understand the signaling cascade after KOR activation in a systematic manner. In this study, an in-depth quantitative phosphoproteomic analysis resulted in 305 phosphosites, which were significantly changed in three KOR-overexpressed cells upon treatment with two KOR agonists. The subsequent substrate-kinase prediction analysis revealed that 18 potential kinases might be activated under stimulation of the agonists. We found that phosphorylation of PAK1/2 (p21-activated kinase 1/2) was induced by KOR agonists, resulting in reduced actin stress fibers and cytoskeletal reorganization. In summary, this quantitative phosphoproteomics-based research studied the downstream phosphorylation events upon KOR activation, which may shed light on the investigations of KOR signaling pathway and targeted therapy for KOR-related diseases.
Agid:
6482720