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

J 2018

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

STRAKOVÁ, Kateřina; M. KOWALSKI-JAHN; Tomáš GYBEĽ; Jana VALNOHOVÁ; V.M. DHOPLE et al.

Základní údaje

Originální název

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

Autoři

Vydání

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2018, 0021-9258

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.106

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/18:00101768

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

DEP DOMAIN; FUNCTIONAL-ANALYSIS; PLANAR POLARITY; BETA-ARRESTINS; DIX DOMAIN; I-EPSILON; RECEPTOR; RECRUITMENT; COMPLEX; GROWTH

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 3. 2019 12:48, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

EE2.3.20.0180, projekt VaV

Název: Spolupráce mezi Masarykovou univerzitou a Karolinska Institutet, Stockholm na poli biomedicíny

GA13-32990S, projekt VaV

Název: Posttranslační modifikace receptorů na buněčném povrchu jako určující faktor pro specificitu signálu

Investor: Grantová agentura ČR, Posttranslační modifikace receptorů na buněčném povrchu jako určující faktor pro specificitu signálu

GA17-16680S, projekt VaV

Název: Nové postupy pro určení aktivity dráhy planární buněčné polarity (PCP)

Investor: Grantová agentura ČR, Nové postupy pro určení aktivity dráhy planární buněčné polarity (PCP)

608180, interní kód MU

Název: WNT-mediated signal relay in stem cells and oncogenesis - from basic biology to applications (Akronym: WntsApp)

Investor: Evropská unie, WNT-mediated signal relay in stem cells and oncogenesis - from basic biology to applications, Lidé

Citovat

STRAKOVÁ, Kateřina; M. KOWALSKI-JAHN; Tomáš GYBEĽ; Jana VALNOHOVÁ; V.M. DHOPLE; Jakub HARNOŠ; Ondřej BERNATÍK; Sri Ranjani GANJI; Zbyněk ZDRÁHAL; J. MULDER; C. LINDSKOG; Vítězslav BRYJA a G. SCHULTE. Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2018, roč. 293, č. 48, s. 18477-18493. ISSN 0021-9258. Dostupné z: https://doi.org/10.1074/jbc.RA118.004656.

@article{1504861,
   author = {Straková, Kateřina and KowalskiandJahn, M. and Gybeľ, Tomáš and Valnohová, Jana and Dhople, V.M. and Harnoš, Jakub and Bernatík, Ondřej and Ganji, Sri Ranjani and Zdráhal, Zbyněk and Mulder, J. and Lindskog, C. and Bryja, Vítězslav and Schulte, G.},
   article_location = {Bethesda, USA},
   article_number = {48},
   doi = {https://doi.org/10.1074/jbc.RA118.004656},
   keywords = {DEP DOMAIN; FUNCTIONAL-ANALYSIS; PLANAR POLARITY; BETA-ARRESTINS; DIX DOMAIN; I-EPSILON; RECEPTOR; RECRUITMENT; COMPLEX; GROWTH},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization},
   volume = {293},
   year = {2018}
}

TY  - JOUR
ID  - 1504861
AU  - Straková, Kateřina - Kowalski-Jahn, M. - Gybeľ, Tomáš - Valnohová, Jana - Dhople, V.M. - Harnoš, Jakub - Bernatík, Ondřej - Ganji, Sri Ranjani - Zdráhal, Zbyněk - Mulder, J. - Lindskog, C. - Bryja, Vítězslav - Schulte, G.
PY  - 2018
TI  - Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization
JF  - Journal of Biological Chemistry
VL  - 293
IS  - 48
SP  - 18477-18493
EP  - 18477-18493
PB  - Amer. Soc. Biochem. Mol. Biol.
SN  - 00219258
KW  - DEP DOMAIN
KW  - FUNCTIONAL-ANALYSIS
KW  - PLANAR POLARITY
KW  - BETA-ARRESTINS
KW  - DIX DOMAIN
KW  - I-EPSILON
KW  - RECEPTOR
KW  - RECRUITMENT
KW  - COMPLEX
KW  - GROWTH
N2  - 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.
ER  -

STRAKOVÁ, Kateřina; M. KOWALSKI-JAHN; Tomáš GYBEĽ; Jana VALNOHOVÁ; V.M. DHOPLE; Jakub HARNOŠ; Ondřej BERNATÍK; Sri Ranjani GANJI; Zbyněk ZDRÁHAL; J. MULDER; C. LINDSKOG; Vítězslav BRYJA a G. SCHULTE. Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2018, roč.~293, č.~48, s.~18477-18493. ISSN~0021-9258. Dostupné z: https://doi.org/10.1074/jbc.RA118.004656.

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