dc.contributor.author
Park, Misun
dc.contributor.author
Reddy, Gopireddy R.
dc.contributor.author
Wallukat, Gerd
dc.contributor.author
Xiang, Yang K.
dc.contributor.author
Steinberg, Susan F.
dc.date.accessioned
2018-06-08T10:22:18Z
dc.date.available
2017-10-12T09:54:21.701Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20308
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23612
dc.description.abstract
β1-adrenergic receptors (β1ARs) mediate catecholamine actions in
cardiomyocytes by coupling to both Gs/cAMP-dependent and Gs-independent
/growth-regulatory pathways. Structural studies of the β1AR define ligand-
binding sites in the transmembrane helices and effector docking sites at the
intracellular surface of the β1AR, but the extracellular N-terminus, which is
a target for post-translational modifications, typically is ignored. This
study identifies β1AR N-terminal O-glycosylation at Ser37/Ser41 as a mechanism
that prevents β1AR N-terminal cleavage. We used an adenoviral overexpression
strategy to show that both full-length/glycosylated β1ARs and N-terminally
truncated glycosylation-defective β1ARs couple to cAMP and ERK-MAPK signaling
pathways in cardiomyocytes. However, a glycosylation defect that results in
N-terminal truncation stabilizes β1ARs in a conformation that is biased toward
the cAMP pathway. The identification of O-glycosylation and N-terminal
cleavage as novel structural determinants of β1AR responsiveness in
cardiomyocytes could be exploited for therapeutic advantage.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Cardiac hypertrophy
dc.subject
Cardiovascular diseases
dc.title
β1-adrenergic receptor O-glycosylation regulates N-terminal cleavage and
signaling responses in cardiomyocytes
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Scientific Reports. - 7 (2017), Artikel Nr. 7890
dc.title.translated
Beta1-adrenergic receptor O-glycosylation regulates N-terminal cleavage and
signaling responses in cardiomyocytes
de
dcterms.bibliographicCitation.doi
10.1038/s41598-017-06607-z
dcterms.bibliographicCitation.url
http://www.nature.com/articles/s41598-017-06607-z
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000028292
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008970
dcterms.accessRights.openaire
open access