Sequential activation and inactivation of dishevelled in the
Wnt/{beta}-catenin pathway by casein kinases.

J 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.

Základní údaje

Originální název

Sequential activation and inactivation of dishevelled in the Wnt/{beta}-catenin pathway by casein kinases.

Autoři

BERNATÍK, Ondřej (203 Česká republika, domácí), Sri Ranjani GANJI (356 Indie, domácí), Jacomijn DIJKSTERHUIS (528 Nizozemské království), Peter KONIK (703 Slovensko), Igor ČERVENKA (703 Slovensko, domácí), Tilman POLONIO (276 Německo), Pavel KREJČÍ (203 Česká republika), Gunnar SCHULTE (276 Německo) a Vítězslav BRYJA (203 Česká republika, garant, domácí)

Vydání

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2011, 0021-9258

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.773

Kód RIV

RIV/00216224:14310/11:00049416

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1074/jbc.M110.169870

UT WoS

000288547000056

Klíčová slova anglicky

Dishevelled; casein kinases; Wnt-beta catenin pathway

Štítky

AKR, rivok, ZR

Změněno: 20. 4. 2012 15:08, Ing. Zdeňka Rašková

Anotace

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.

Návaznosti

GA204/09/0498, projekt VaV

Název: Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování

Investor: Grantová agentura ČR, Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování

GD204/09/H058, projekt VaV

Název: Mezibuněčná signalizace ve vývoji organismu a vzniku onemocnění

Investor: Grantová agentura ČR, Mezibuněčná signalizace ve vývoji organismu a vzniku onemocnění

KJB501630801, projekt VaV

Název: Posttranslační modifikace proteinu Dishevelled

Investor: Akademie věd ČR, Posttranslační modifikace proteinu Dishevelled

MSM0021622430, záměr

Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Citovat

BERNATÍK, Ondřej, Sri Ranjani GANJI, Jacomijn DIJKSTERHUIS, Peter KONIK, Igor ČERVENKA, Tilman POLONIO, Pavel KREJČÍ, Gunnar SCHULTE a Vítězslav BRYJA. Sequential activation and inactivation of dishevelled in the Wnt/{beta}-catenin pathway by casein kinases. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2011, roč. 286, č. 12, s. 10396-10410. ISSN 0021-9258. Dostupné z: https://dx.doi.org/10.1074/jbc.M110.169870.

@article{929228,
   author = {Bernatík, Ondřej and Ganji, Sri Ranjani and Dijksterhuis, Jacomijn and Konik, Peter and Červenka, Igor and Polonio, Tilman and Krejčí, Pavel and Schulte, Gunnar and Bryja, Vítězslav},
   article_location = {Bethesda, USA},
   article_number = {12},
   doi = {http://dx.doi.org/10.1074/jbc.M110.169870},
   keywords = {Dishevelled; casein kinases; Wnt-beta catenin pathway},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {Sequential activation and inactivation of dishevelled in the Wnt/{beta}-catenin pathway by casein kinases.},
   volume = {286},
   year = {2011}
}

TY  - JOUR
ID  - 929228
AU  - Bernatík, Ondřej - Ganji, Sri Ranjani - Dijksterhuis, Jacomijn - Konik, Peter - Červenka, Igor - Polonio, Tilman - Krejčí, Pavel - Schulte, Gunnar - Bryja, Vítězslav
PY  - 2011
TI  - Sequential activation and inactivation of dishevelled in the Wnt/{beta}-catenin pathway by casein kinases.
JF  - Journal of Biological Chemistry
VL  - 286
IS  - 12
SP  - 10396-10410
EP  - 10396-10410
PB  - Amer. Soc. Biochem. Mol. Biol.
SN  - 00219258
KW  - Dishevelled
KW  - casein kinases
KW  - Wnt-beta catenin pathway
N2  - 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.
ER  -

BERNATÍK, Ondřej, Sri Ranjani GANJI, Jacomijn DIJKSTERHUIS, Peter KONIK, Igor ČERVENKA, Tilman POLONIO, Pavel KREJČÍ, Gunnar SCHULTE a Vítězslav BRYJA. Sequential activation and inactivation of dishevelled in the Wnt/$\{$beta$\}$-catenin pathway by casein kinases. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2011, roč.~286, č.~12, s.~10396-10410. ISSN~0021-9258. Dostupné z: https://dx.doi.org/10.1074/jbc.M110.169870.

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