Detailed Information on Publication Record
2011
Sequential activation and inactivation of dishevelled in the Wnt/{beta}-catenin pathway by casein kinases.
BERNATÍK, Ondřej, Sri Ranjani GANJI, Jacomijn DIJKSTERHUIS, Peter KONIK, Igor ČERVENKA et. al.Basic information
Original name
Sequential activation and inactivation of dishevelled in the Wnt/{beta}-catenin pathway by casein kinases.
Authors
BERNATÍK, Ondřej (203 Czech Republic, belonging to the institution), Sri Ranjani GANJI (356 India, belonging to the institution), Jacomijn DIJKSTERHUIS (528 Netherlands), Peter KONIK (703 Slovakia), Igor ČERVENKA (703 Slovakia, belonging to the institution), Tilman POLONIO (276 Germany), Pavel KREJČÍ (203 Czech Republic), Gunnar SCHULTE (276 Germany) and Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution)
Edition
Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2011, 0021-9258
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
Impact factor
Impact factor: 4.773
RIV identification code
RIV/00216224:14310/11:00049416
Organization unit
Faculty of Science
UT WoS
000288547000056
Keywords in English
Dishevelled; casein kinases; Wnt-beta catenin pathway
Změněno: 20/4/2012 15:08, Ing. Zdeňka Rašková
Abstract
V originále
Dishevelled (Dvl) is a key component in the Wnt/beta-catenin signaling pathway. Dvl can multimerize to form dynamic protein aggregates, which are required for the activation of downstream signaling. Upon pathway activation by Wnts, Dvl becomes phosphorylated to yield phosphorylated and shifted-(PS) Dvl. Both activation of Dvl in Wnt/beta-catenin signaling and Wnt-induced PS-Dvl formation are dependent on casein kinase 1 (CK1)delta/epsilon activity. However, the overexpression of CK1 was shown to dissolve Dvl aggregates and endogenous PS-Dvl forms irrespective of whether or not the activating Wnt triggers the Wnt/beta-catenin pathway. Using a combination of gain-of-function, loss-of-function and domain mapping approaches, we attempted to solve this discrepancy regarding the role of CK1epsilon in Dvl biology. We analyzed mutual interaction of CK1delta/epsilon and two other Dvl kinases, CK2 and PAR1, in Wnt/beta-catenin pathway. We show that CK2 acts as a constitutive kinase, whose activity is required for the further action of CK1epsilon. Furthermore, we demonstrate that the two consequences of CK1epsilon phosphorylation are separated both spatially and functionally: First, CK1epsilon-mediated induction of TCF/LEF-driven transcription (associated with dynamic recruitment of Axin1) is mediated via a PDZ-proline-rich region of Dvl. Second, CK1epsilon-mediated formation of PS-Dvl is mediated by the Dvl3 C-terminus. Further, we demonstrate with several methods that PS-Dvl has decreased ability to polymerize with other Dvls and could thus act as the inactive signaling intermediate. We propose a multistep and multikinase model for Dvl activation in the Wnt/beta-catenin pathway, which uncovers a built-in de-activation mechanism that is triggered by activating phosphorylation of Dvl by CK1delta/epsilon.
Links
| GA204/09/0498, research and development project |
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| GD204/09/H058, research and development project |
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| KJB501630801, research and development project |
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| MSM0021622430, plan (intention) |
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