Proteomics

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Dynamic phosphoproteomics of BRS3 activation reveals Hippo signaling pathway for cell migration


ABSTRACT: Bombesin receptor subtype-3 (BRS3) is an orphan G-protein coupled receptor (GPCR) that involved in a range of pathological and physiological processes, while its biological functions and underlying regulatory mechanisms remain largely unknown. Quantitative phosphoproteomics approach was employed in this study to comprehensively decipher the signal transductions that occurred upon intracellular BRS3 activation. Lung cancer cell line H1299-BRS3 was treated with MK-5046, an agonist of BRS3, for different durations. Harvested cellular proteins were digested and phosphopeptides were enriched by immobilized titanium (IV) ion affinity chromatography (Ti4+-IMAC) for label-free quantification analysis. In total, 12,052 phosphopeptides were identified, corresponding to 4,015 phosphoproteins and 10,820 phosphosites. Data analysis revealed that 27 phosphopeptides corresponding to 6 proteins were involved in Hippo signaling pathway, which was significantly regulated by the activation of BRS3. Verification experiments demonstrated down-regulation of Hippo signaling pathway could induce the dephosphorylation and nucleus localization of Yes-associated protein (YAP), which further confirmed its association with cell migration through kinase inhibition. Our data collectively demonstrate that BRS3 activation contributes to cell migration through down-regulating Hippo signaling pathway.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: miao guo  

LAB HEAD: Hua xiao

PROVIDER: PXD035666 | Pride | 2023-07-12

REPOSITORIES: Pride

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Action DRS
YP202127387-GM-0-1.raw Raw
YP202127387-GM-0-2.raw Raw
YP202127387-GM-0-3.raw Raw
YP202127387-GM-10-1.raw Raw
YP202127387-GM-10-2.raw Raw
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Publications

Dynamic Phosphoproteomics of BRS3 Activation Reveals the Hippo Signaling Pathway for Cell Migration.

Guo Miao M   Zhang Yan Y   Wu Lehao L   Sheng Ye Y   Zhao Jiaqi J   Wang Zeyuan Z   Wang Huiyu H   Zhang Lu L   Xiao Hua H  

Journal of proteome research 20230627 7


Bombesin receptor subtype-3 (BRS3) is an orphan G-protein coupled receptor (GPCR) that is involved in a variety of pathological and physiological processes, while its biological functions and underlying regulatory mechanisms remain largely unknown. In this study, a quantitative phosphoproteomics approach was employed to comprehensively decipher the signal transductions that occurred upon intracellular BRS3 activation. The lung cancer cell line H1299-BRS3 was treated with MK-5046, an agonist of B  ...[more]

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