Informace o projektu
Posttranslační modifikace receptorů na buněčném povrchu jako určující faktor pro specificitu signálu
- Kód projektu
- GA13-32990S
- Období řešení
- 2/2013 - 12/2015
- Investor / Programový rámec / typ projektu
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Grantová agentura ČR
- Standardní projekty
- Fakulta / Pracoviště MU
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Přírodovědecká fakulta
- Prof. Gunnar Schulte, PhD.
- Mgr. Kateřina Straková, Ph.D.
Cell surface receptors orchestrate communication based on ligands, such as hormones. Here, we focus on Frizzled (FZD) receptors, which in combination with their ligands - the WNTs - are crucial during embryogenesis. FZD signaling is required for embryonic patterning, convergent extension movements, and stem cell regulation, however, little is known about how WNTs accomplish specificity in their responses. We do not, however, focus on downstream signaling but rather on the receptor signature driving signaling specificity. We will identify FZD phosphorylation patterns biochemically and by mass spectrometry and relate them to signaling outcome. Upon mapping of FZD phosphorylation "barcodes" we screen for phospho-selective /pathway-specific FZD antibodies by a phage-display-based approach. The antibodies will be validated thoroughly and used for in vivo mapping of FZD phosphorylation during mouse embryonic development. Labeling of WNTs and selected, pathway-specific phospho-FZD antibodies in mouse embryos will then reveal a unique picture of WNT/FZD signaling in 3D over time.
Publikace
Počet publikací: 7
2018
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Dishevelled enables casein kinase 1-mediated phosphorylation of Frizzled 6 required for cell membrane localization
Journal of Biological Chemistry, rok: 2018, ročník: 293, vydání: 48, DOI
2017
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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, rok: 2017, ročník: 38, vydání: October, DOI
2016
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Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins
Proceedings of the National Academy of Sciences of the United States of America, rok: 2016, ročník: 113, vydání: 33, DOI
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WNT Stimulation Dissociates a Frizzled 4 Inactive-State Complex with G alpha(12/13)
Molecular Pharmacology, rok: 2016, ročník: 90, vydání: 4, DOI
2015
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Asymmetry of VANGL2 in migrating lymphocytes as a tool to monitor activity of the mammalian WNT/planar cell polarity pathway
Journal of Cell Communication and Signaling, rok: 2015, ročník: 13, vydání: January, DOI
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Frizzleds and WNT/beta-catenin signaling - The black box of ligand-receptor selectivity, complex stoichiometry and activation kinetics
European Journal of Pharmacology, rok: 2015, ročník: 763, vydání: September, DOI
2014
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Disheveled regulates precoupling of heterotrimeric G proteins to Frizzled 6
FASEB JOURNAL, rok: 2014, ročník: 28, vydání: 5, DOI