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. (C) 2019 Elsevier Inc. All rights reserved.
[1]Shanghai Univ, Sch Life Sci, Shanghai, Peoples R China.
[2]Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai, Peoples R China.
[3]Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China.
[4]Univ Chinese Acad Sci, Beijing, Peoples R China.
[5]Shanghai Univ Tradit Chinese Med, E Inst, Shanghai Municipal Educ Comm, Shanghai, Peoples R China.
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