Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F18%3A00101768" target="_blank" >RIV/00216224:14310/18:00101768 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1074/jbc.RA118.004656" target="_blank" >http://dx.doi.org/10.1074/jbc.RA118.004656</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA118.004656" target="_blank" >10.1074/jbc.RA118.004656</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization

Popis výsledku v původním jazyce

Frizzleds (FZDs) are receptors for secreted lipoglycoproteins of the Wingless/Int-1(WNT) family, initiating an important signal transduction network in multicellular organisms. FZDs are G protein-coupled receptors (GPCRs), which are well known to be regulated by phosphorylation, leading to specific downstream signaling or receptor desensitization. The role and underlying mechanisms of FZD phosphorylation remain largely unexplored. Here, we investigated the phosphorylation of human FZD(6). Using MS analysis and a phospho-state- and -site-specific antibody, we found that Ser-648, located in the FZD(6) C terminus, is efficiently phosphorylated by casein kinase 1 is an element of (CK1 is an element of) and that this phosphorylation requires the scaffolding protein Dishevelled (DVL). In an overexpression system, DVL1, -2, and -3 promoted CK1-mediated FZD(6) phosphorylation on Ser-648. This DVL activity required an intact DEP domain and FZD-mediated recruitment of this domain to the cell membrane. Substitution of the CK1 is an element of-targeted phosphomo-tif reduced FZD(6) surface expression, suggesting that Ser-648 phosphorylation controls membrane trafficking of FZD(6). Phos-pho-Ser-648 FZD(6) immunoreactivity in human fallopian tube epithelium was predominantly apical, associated with cilia in a subset of epithelial cells, compared with the total FZD(6) protein expression, suggesting that FZD(6) phosphorylation contributes to asymmetric localization of receptor function within the cell and to epithelial polarity. Given the key role of FZD(6) in planar cell polarity, our results raise the possibility that asymmetric phosphorylation of FZD(6) rather than asymmetric protein distribution accounts for polarized receptor signaling.

Název v anglickém jazyce

Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization

Popis výsledku anglicky

Frizzleds (FZDs) are receptors for secreted lipoglycoproteins of the Wingless/Int-1(WNT) family, initiating an important signal transduction network in multicellular organisms. FZDs are G protein-coupled receptors (GPCRs), which are well known to be regulated by phosphorylation, leading to specific downstream signaling or receptor desensitization. The role and underlying mechanisms of FZD phosphorylation remain largely unexplored. Here, we investigated the phosphorylation of human FZD(6). Using MS analysis and a phospho-state- and -site-specific antibody, we found that Ser-648, located in the FZD(6) C terminus, is efficiently phosphorylated by casein kinase 1 is an element of (CK1 is an element of) and that this phosphorylation requires the scaffolding protein Dishevelled (DVL). In an overexpression system, DVL1, -2, and -3 promoted CK1-mediated FZD(6) phosphorylation on Ser-648. This DVL activity required an intact DEP domain and FZD-mediated recruitment of this domain to the cell membrane. Substitution of the CK1 is an element of-targeted phosphomo-tif reduced FZD(6) surface expression, suggesting that Ser-648 phosphorylation controls membrane trafficking of FZD(6). Phos-pho-Ser-648 FZD(6) immunoreactivity in human fallopian tube epithelium was predominantly apical, associated with cilia in a subset of epithelial cells, compared with the total FZD(6) protein expression, suggesting that FZD(6) phosphorylation contributes to asymmetric localization of receptor function within the cell and to epithelial polarity. Given the key role of FZD(6) in planar cell polarity, our results raise the possibility that asymmetric phosphorylation of FZD(6) rather than asymmetric protein distribution accounts for polarized receptor signaling.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

—

Svazek periodika

293

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

18477-18493

Kód UT WoS článku

000458467300006

EID výsledku v databázi Scopus

2-s2.0-85057526464