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

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Publikace nespadá pod Pedagogickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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STRAKOVÁ Kateřina MATRICON Pierre YOKOTA Chika ARTHOFER Elisa BERNATÍK Ondřej RODRIGUEZ David ARENAS CASES Ernesto CARLSSON Jens BRYJA Vítězslav SCHULTE Gunnar

Rok publikování 2017
Druh Článek v odborném periodiku
Časopis / Zdroj Cellular Signalling
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www http://www.sciencedirect.com/science/article/pii/S0898656817301766?via%3Dihub
Doi http://dx.doi.org/10.1016/j.cellsig.2017.06.018
Obor Fyziologie
Klíčová slova Disheveled; DVL2; Frizzled; FZD(4); GNA12; GNA13
Popis 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.
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