TY - JOUR
T1 - Ligands can differentially and temporally modulate GPCR interaction with 14-3-3 isoforms
AU - Eishingdrelo, Haifeng
AU - Qin, Xiaofa
AU - Yuan, Luwa
AU - Kongsamut, Sathapana
AU - Yu, Lei
N1 - Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Haifeng Eishingdrelo reports financial support was provided by National Institutes of Health. Haifeng Eishingdrelo reports a relationship with BioInvenu Corporation that includes: board membership, employment, equity or stocks, and funding grants. Haifeng Eishingdrelo has patent licensed to BioInvenu.
Funding Information:
This work is supported by NIH SBIR grants 2R44MH108203 and 1R43DA050264 to H.E.
Publisher Copyright:
© 2022 The Authors
PY - 2022/1
Y1 - 2022/1
N2 - GPCR signaling and function depend on their associated proteins and subcellular locations. Besides G-proteins and β-arrestins, 14-3-3 proteins participate in GPCR trafficking and signaling, and they connect a large number of diverse proteins to form signaling networks. Multiple 14-3-3 isoforms exist, and a GPCR can differentially interact with different 14-3-3 isoforms in response to agonist treatment. We found that some agonist-induced GPCR/14-3-3 signal intensities can rapidly decrease. We confirmed that this phenomenon of rapidly decreasing agonist-induced GPCR/14-3-3 signal intensity could also be paralleled with GPCR/β-arrestin-2 signals, indicating diminished levels of GPCR/signal adaptor complexes during endocytosis. The temporal signals could implicate either GPCR/14-3-3 complex dissociation or the complex undergoing a degradation process. Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting a new approach for GPCR drug development by modulating GPCR/14-3-3 signals temporally.
AB - GPCR signaling and function depend on their associated proteins and subcellular locations. Besides G-proteins and β-arrestins, 14-3-3 proteins participate in GPCR trafficking and signaling, and they connect a large number of diverse proteins to form signaling networks. Multiple 14-3-3 isoforms exist, and a GPCR can differentially interact with different 14-3-3 isoforms in response to agonist treatment. We found that some agonist-induced GPCR/14-3-3 signal intensities can rapidly decrease. We confirmed that this phenomenon of rapidly decreasing agonist-induced GPCR/14-3-3 signal intensity could also be paralleled with GPCR/β-arrestin-2 signals, indicating diminished levels of GPCR/signal adaptor complexes during endocytosis. The temporal signals could implicate either GPCR/14-3-3 complex dissociation or the complex undergoing a degradation process. Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting a new approach for GPCR drug development by modulating GPCR/14-3-3 signals temporally.
KW - 14-3-3 proteins
KW - G-protein coupled receptor (GPCR)
KW - Protein-protein interaction
KW - Receptor trafficking
KW - Signal transduction
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U2 - 10.1016/j.crphar.2022.100123
DO - 10.1016/j.crphar.2022.100123
M3 - Article
AN - SCOPUS:85135874071
SN - 2590-2571
VL - 3
JO - Current Research in Pharmacology and Drug Discovery
JF - Current Research in Pharmacology and Drug Discovery
M1 - 100123
ER -