dc.contributor.author |
Tóth, András |
|
dc.contributor.author |
Prokop, Susanne Clare |
|
dc.contributor.author |
Gyombolai, Pál |
|
dc.contributor.author |
Várnai, Péter |
|
dc.contributor.author |
Balla, András |
|
dc.contributor.author |
Gurevich, Vsevolod V |
|
dc.contributor.author |
Hunyady, László |
|
dc.contributor.author |
Turu, Gábor |
|
dc.date.accessioned |
2018-02-27T10:06:03Z |
|
dc.date.available |
2018-02-27T10:06:03Z |
|
dc.date.issued |
2018 |
|
dc.identifier |
85040996028 |
|
dc.identifier.citation |
pagination=876-892;
journalVolume=293;
journalIssueNumber=3;
journalTitle=JOURNAL OF BIOLOGICAL CHEMISTRY; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/4730 |
|
dc.identifier.uri |
doi:10.1074/jbc.M117.813139 |
|
dc.description.abstract |
-Arrestins are key regulators and signal transducers of G protein– coupled receptors (GPCRs). The interaction between receptors and -arrestins is generally believed to require both receptor activity and phosphorylation by GPCR kinases. In this study, we investigated whether -arrestins are able to bind second messenger kinase–phosphorylated, but inactive receptors as well. Because heterologous phosphorylation is a common phenomenon among GPCRs, this mode of -arrestin activation may represent a novel mechanism of signal transduction and receptor cross-talk. Here we demonstrate that activation of protein kinase C (PKC) by phorbol myristate acetate, Gq/11-coupled GPCR, or epidermal growth factor receptor stimulation promotes -arrestin2 recruitment to unliganded AT1 angiotensin receptor (AT1R). We found that this interaction depends on the stability lock, a structure responsible for the sustained binding between GPCRs and -arrestins, formed by phosphorylated serine–threonine clusters in the receptor’s C terminus and two conserved phosphate-binding lysines in the -arrestin2 N-domain. Using improved FlAsH-based serine-threonine clusters -arrestin2 conformational biosensors, we also show that the stability lock not only stabilizes the receptor–-arrestin interaction, but also governs the structural rearrangements within -arrestins. Furthermore, we found that -arrestin2 binds to PKC-phosphorylated AT1R in a distinct active conformation, which triggers MAPK recruitment and receptor internalization. Our results provide new insights into the activation of -arrestins and reveal their novel role in receptor cross-talk. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. |
|
dc.relation.ispartof |
urn:issn:0021-9258 |
|
dc.title |
Heterologous phosphorylation–induced formation of a stability lock permits regulation of inactive receptors by beta-arrestins |
|
dc.type |
Journal Article |
|
dc.date.updated |
2018-02-08T08:52:59Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
3331109 |
|
dc.contributor.department |
SE/AOK/I/Élettani Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|