The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.

The human leukocyte adhesion-G protein-coupled receptors (GPCRs), the epidermal growth factor (EGF)-TM7 proteins, are shown here to function as homo- and hetero-oligomers. Using cell surface cross-linking, co-immunoprecipitation, and fluorescence resonance energy transfer analysis of EMR2, an EGF-TM...

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Main Authors: Davies, J, Chang, G, Yona, S, Gordon, S, Stacey, M, Lin, H
Format: Journal article
Language:English
Published: 2007
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author Davies, J
Chang, G
Yona, S
Gordon, S
Stacey, M
Lin, H
author_facet Davies, J
Chang, G
Yona, S
Gordon, S
Stacey, M
Lin, H
author_sort Davies, J
collection OXFORD
description The human leukocyte adhesion-G protein-coupled receptors (GPCRs), the epidermal growth factor (EGF)-TM7 proteins, are shown here to function as homo- and hetero-oligomers. Using cell surface cross-linking, co-immunoprecipitation, and fluorescence resonance energy transfer analysis of EMR2, an EGF-TM7 receptor predominantly expressed in myeloid cells, we demonstrate that it forms dimers in a reaction mediated exclusively by the TM7 moiety. We have also identified a naturally occurring but structurally unstable EMR2 splice variant that acts as a dominant negative modulator by dimerizing with the wild type receptor and down-regulating its expression. Additionally, heterodimerization between closely related EGF-TM7 members is shown to result in the modulation of expression and ligand binding properties of the receptors. These findings suggest that receptor homo- and hetero-oligomerization play a regulatory role in modulating the expression and function of leukocyte adhesion-GPCRs.
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spelling oxford-uuid:929c8834-fc5c-42de-a3ec-9953aa0d18e02022-03-26T23:26:44ZThe role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:929c8834-fc5c-42de-a3ec-9953aa0d18e0EnglishSymplectic Elements at Oxford2007Davies, JChang, GYona, SGordon, SStacey, MLin, HThe human leukocyte adhesion-G protein-coupled receptors (GPCRs), the epidermal growth factor (EGF)-TM7 proteins, are shown here to function as homo- and hetero-oligomers. Using cell surface cross-linking, co-immunoprecipitation, and fluorescence resonance energy transfer analysis of EMR2, an EGF-TM7 receptor predominantly expressed in myeloid cells, we demonstrate that it forms dimers in a reaction mediated exclusively by the TM7 moiety. We have also identified a naturally occurring but structurally unstable EMR2 splice variant that acts as a dominant negative modulator by dimerizing with the wild type receptor and down-regulating its expression. Additionally, heterodimerization between closely related EGF-TM7 members is shown to result in the modulation of expression and ligand binding properties of the receptors. These findings suggest that receptor homo- and hetero-oligomerization play a regulatory role in modulating the expression and function of leukocyte adhesion-GPCRs.
spellingShingle Davies, J
Chang, G
Yona, S
Gordon, S
Stacey, M
Lin, H
The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.
title The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.
title_full The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.
title_fullStr The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.
title_full_unstemmed The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.
title_short The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.
title_sort role of receptor oligomerization in modulating the expression and function of leukocyte adhesion g protein coupled receptors
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