The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif
important for structural integrity of the receptor and
recruitment of Disheveled.

J 2017

The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled.

STRAKOVÁ, Kateřina, Pierre MATRICON, Chika YOKOTA, Elisa ARTHOFER, Ondřej BERNATÍK et. al.

Basic information

Original name

The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled.

Authors

STRAKOVÁ, Kateřina (203 Czech Republic, belonging to the institution), Pierre MATRICON (752 Sweden), Chika YOKOTA (752 Sweden), Elisa ARTHOFER (840 United States of America), Ondřej BERNATÍK (203 Czech Republic, belonging to the institution), David RODRIGUEZ (752 Sweden), Ernesto ARENAS CASES (752 Sweden), Jens CARLSSON (752 Sweden), Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution) and Gunnar SCHULTE (276 Germany, belonging to the institution)

Edition

Cellular Signalling, New York, ELSEVIER SCIENCE, 2017, 0898-6568

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.487

RIV identification code

RIV/00216224:14310/17:00095350

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.cellsig.2017.06.018

UT WoS

000408788800009

Keywords in English

Disheveled; DVL2; Frizzled; FZD(4); GNA12; GNA13

Abstract

V originále

Frizzleds (FZDs) are unconventional G protein-coupled receptors, which activate diverse intracellular signaling pathways via the phosphoprotein Disheveled (DVL) and heterotrimeric G proteins. The interaction interplay of FZDs with DVL and G proteins is complex, involves different regions of FZD and the potential dynamics are poorly understood. In the present study, we aimed to characterize the function of a highly conserved tyrosine (Y2502.39) in the intracellular loop 1 (IL1) of human FZD4. We have found Y2502.39 to be crucial for DVL2 interaction and DVL2 translocation to the plasma membrane. Mutant FZD4-Y2502.39F, impaired in DVL2 binding, was defective in both beta-catenin-dependent and beta-catenin-independent WNT signaling induced in Xenopus laevis embryos. The same mutant maintained interaction with the heterotrimeric G proteins Galfa12 and Galfa13 and was able to mediate WNT-induced G protein dissociation and G protein-dependent YAP/TAZ signaling. We conclude from modeling and dynamics simulation efforts that Y2502.39 is important for the structural integrity of the FZD-DVL, but not for the FZD-G protein interface and hypothesize that the interaction network of Y2502.39 and H3484.46 plays a role in specifying downstream signaling pathways induced by the receptor.

Links

EE2.3.20.0180, research and development project

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

GA13-32990S, research and development project

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

Investor: Czech Science Foundation

Citovat

STRAKOVÁ, Kateřina, Pierre MATRICON, Chika YOKOTA, Elisa ARTHOFER, Ondřej BERNATÍK, David RODRIGUEZ, Ernesto ARENAS CASES, Jens CARLSSON, Vítězslav BRYJA and Gunnar SCHULTE. The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled. Cellular Signalling. New York: ELSEVIER SCIENCE, 2017, vol. 38, October, p. 85-96. ISSN 0898-6568. Available from: https://dx.doi.org/10.1016/j.cellsig.2017.06.018.

@article{1402056,
   author = {Straková, Kateřina and Matricon, Pierre and Yokota, Chika and Arthofer, Elisa and Bernatík, Ondřej and Rodriguez, David and Arenas Cases, Ernesto and Carlsson, Jens and Bryja, Vítězslav and Schulte, Gunnar},
   article_location = {New York},
   article_number = {October},
   doi = {http://dx.doi.org/10.1016/j.cellsig.2017.06.018},
   keywords = {Disheveled; DVL2; Frizzled; FZD(4); GNA12; GNA13},
   language = {eng},
   issn = {0898-6568},
   journal = {Cellular Signalling},
   title = {The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled.},
   url = {http://www.sciencedirect.com/science/article/pii/S0898656817301766?via%3Dihub},
   volume = {38},
   year = {2017}
}

TY  - JOUR
ID  - 1402056
AU  - Straková, Kateřina - Matricon, Pierre - Yokota, Chika - Arthofer, Elisa - Bernatík, Ondřej - Rodriguez, David - Arenas Cases, Ernesto - Carlsson, Jens - Bryja, Vítězslav - Schulte, Gunnar
PY  - 2017
TI  - The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled.
JF  - Cellular Signalling
VL  - 38
IS  - October
SP  - 85-96
EP  - 85-96
PB  - ELSEVIER SCIENCE
SN  - 08986568
KW  - Disheveled
KW  - DVL2
KW  - Frizzled
KW  - FZD(4)
KW  - GNA12
KW  - GNA13
UR  - http://www.sciencedirect.com/science/article/pii/S0898656817301766?via%3Dihub
L2  - http://www.sciencedirect.com/science/article/pii/S0898656817301766?via%3Dihub
N2  - Frizzleds (FZDs) are unconventional G protein-coupled receptors, which activate diverse intracellular signaling pathways via the phosphoprotein Disheveled (DVL) and heterotrimeric G proteins. The interaction interplay of FZDs with DVL and G proteins is complex, involves different regions of FZD and the potential dynamics are poorly understood. In the present study, we aimed to characterize the function of a highly conserved tyrosine (Y2502.39) in the intracellular loop 1 (IL1) of human FZD4. We have found Y2502.39 to be crucial for DVL2 interaction and DVL2 translocation to the plasma membrane. Mutant FZD4-Y2502.39F, impaired in DVL2 binding, was defective in both beta-catenin-dependent and beta-catenin-independent WNT signaling induced in Xenopus laevis embryos. The same mutant maintained interaction with the heterotrimeric G proteins Galfa12 and Galfa13 and was able to mediate WNT-induced G protein dissociation and G protein-dependent YAP/TAZ signaling. We conclude from modeling and dynamics simulation efforts that Y2502.39 is important for the structural integrity of the FZD-DVL, but not for the FZD-G protein interface and hypothesize that the interaction network of Y2502.39 and H3484.46 plays a role in specifying downstream signaling pathways induced by the receptor.
ER  -

STRAKOVÁ, Kateřina, Pierre MATRICON, Chika YOKOTA, Elisa ARTHOFER, Ondřej BERNATÍK, David RODRIGUEZ, Ernesto ARENAS CASES, Jens CARLSSON, Vítězslav BRYJA and Gunnar SCHULTE. The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled. \textit{Cellular Signalling}. New York: ELSEVIER SCIENCE, 2017, vol.~38, October, p.~85-96. ISSN~0898-6568. Available from: https://dx.doi.org/10.1016/j.cellsig.2017.06.018.

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