The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled.
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F17%3A00095350" target="_blank" >RIV/00216224:14310/17:00095350 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0898656817301766?via%3Dihub" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0898656817301766?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cellsig.2017.06.018" target="_blank" >10.1016/j.cellsig.2017.06.018</a>
Alternative languages
Result language
angličtina
Original language name
The tyrosine Y250 2.39 in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled.
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular Signalling
ISSN
0898-6568
e-ISSN
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Volume of the periodical
38
Issue of the periodical within the volume
October
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
85-96
UT code for WoS article
000408788800009
EID of the result in the Scopus database
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