Identifying a Neuromedin U Receptor 2 Splice Variant and Determining Its Roles in the Regulation of Signaling and Tumorigenesis In Vitro

PloS One
Ting-Yu LinChing-Wei Luo

Abstract

Neuromedin U (NMU) activates two G protein-coupled receptors, NMUR1 and NMUR2; this signaling not only controls many physiological responses but also promotes tumorigenesis in diverse tissues. We recently identified a novel truncated NMUR2 derived by alternative splicing, namely NMUR2S, from human ovarian cancer cDNA. Sequence analysis, cell surface ELISA and immunocytochemical staining using 293T cells indicated that NMUR2S can be expressed well on the cell surface as a six-transmembrane protein. Receptor pull-down and fluorescent resonance energy transfer assays demonstrated that NMUR1, NMUR2 and this newly discovered NMUR2S can not only form homomeric complexes but also heteromeric complexes with each other. Although not activated by NMU itself, functional assay in combination with receptor quantification and radio-ligand binding in 293T cells indicated that NMUR2S does not alter the translocation and stability of NMUR1 or NMUR2, but rather effectively dampens their signaling by blocking their NMU binding capability through receptor heterodimerization. We further demonstrated that NMU signaling is significantly up-regulated in human ovarian cancers, whereas expression of NMUR2S can block endogenous NMU signaling and further ...Continue Reading

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Feb 21, 2013·American Journal of Physiology. Endocrinology and Metabolism·Ting-Yu LinChing-Wei Luo

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Citations

Sep 8, 2019·Cancers·Patrycja PrzygodzkaJoanna Boncela
Aug 3, 2021·Disease Markers·Yan Tang, Chunsheng Hu

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Methods Mentioned

BETA
PCR
transfection
fluorescence resonance
FRET
pull-down
ELISA
glycosylation

Software Mentioned

TMHMM

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