PXD042449-1

PXD042449 is an original dataset announced via ProteomeXchange.

Title	Activation of dimerized BRS3-EP3 suppresses melanoma cell migration through coupling Gαs protein
Description	The mechanism underlying the crosstalk between Gαq-coupled bombesin receptor subtype-3 (BRS3) and Gαi-coupled E-prostanoid 3 receptor (EP3) remains unknown. Here, we report that BRS3 and EP3 form dimers in the membrane of living HEK-293T cells. Interestingly, we found that BRS3-EP3 dimers switched to couple Gαs protein upon PGE2 stimulation, which provoked the accumulation of cAMP and enhanced the phosphorylation of P38. Quantitative proteomics analysis revealed that the activation of BRS3-EP3 dimers was associated with cell migration. B16 melanoma cell line, which endogenously expresses BRS3 and EP3, was selected to investigate the function of BRS3-EP3 dimers. Results demonstrated that the presence of BRS3 inhibited the migration of B16 melanoma cells upon PGE2 stimulation using scratch-wound assay. Utilizing inhibitors of Gαs and P38, we found that BRS3 interacted with EP3 and switched to couple Gαs protein, causing P38 phosphorylation to inhibit F-actin rearrangement and ultimately suppresses cell migration. Our study reveals the crosstalk between the orphan receptor BRS3 and EP3, and provides a potential novel target for disease treatment.
HostingRepository	PRIDE
AnnounceDate	2026-01-05
AnnouncementXML	Submission_2026-01-04_16:27:11.774.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zeyuan Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-23 18:03:17	ID requested
⏵ 1	2026-01-04 16:27:12	announced

Wang Z, Wu L, Guo M, Zhu J, Zhao J, Wu Y, Xiao H, Zhang Y, protein. Fundam Res, 5(6):2657-2670(2025) [pubmed]

10.1016/j.fmre.2024.04.015;

submitter keyword: Bombesin receptor subtype-3, E-prostanoid 3 receptor, Cell migration, Proteomics,G-protein-coupled receptors dimerization

Hua Xiao
contact affiliation	Shanghai Jiao Tong University
contact email	huaxiao@sjtu.edu.cn
lab head
Zeyuan Wang
contact affiliation	Shanghai Jiaotong University
contact email	zeyuanwang@sjtu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042449
     1. Label: PRIDE project
     2. Name: Activation of dimerized BRS3-EP3 suppresses melanoma cell migration through coupling Gαs protein