Phosphorylation of multiple proteins involved in ciliogenesis
by Tau Tubulin Kinase 2

J 2020

Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2

BERNATÍK, Ondřej, Petra PEJŠKOVÁ, David VYSLOUŽIL, Kateřina HANÁKOVÁ, Zbyněk ZDRÁHAL et. al.

Základní údaje

Originální název

Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2

Autoři

BERNATÍK, Ondřej (203 Česká republika, domácí), Petra PEJŠKOVÁ (203 Česká republika, domácí), David VYSLOUŽIL (203 Česká republika, domácí), Kateřina HANÁKOVÁ (203 Česká republika, domácí), Zbyněk ZDRÁHAL (203 Česká republika, domácí) a Lukáš ČAJÁNEK (203 Česká republika, garant, domácí)

Vydání

Molecular Biology of the Cell, Bethesda, The American Society for Cell Biology, 2020, 1059-1524

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.138

Kód RIV

RIV/00216224:14110/20:00114077

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1091/mbc.E19-06-0334

UT WoS

000530664800004

Klíčová slova anglicky

INTRINSICALLY DISORDERED PROTEIN; PRIMARY CILIA; SUBSTRATE DETERMINANTS; MOTHER CENTRIOLE; EARLY STEPS; TTBK2; DOCKING; ATAXIA; CEP164; MUTATIONS

Štítky

14110517, CF CELLIM, CF PROT, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 11. 2024 20:29, Ing. Martina Blahová

Anotace

V originále

Primary cilia are organelles necessary for proper implementation of developmental and homeostasis processes. To initiate their assembly, coordinated actions of multiple proteins are needed. Tau tubulin kinase 2 (TTBK2) is a key player in the cilium assembly pathway, controlling the final step of cilia initiation. The function of TTBK2 in ciliogenesis is critically dependent on its kinase activity; however, the precise mechanism of TTBK2 action has so far not been fully understood due to the very limited information about its relevant substrates. In this study, we demonstrate that CEP83, CEP89, CCDC92, Rabin8, and DVL3 are substrates of TTBK2 kinase activity. Further, we characterize a set of phosphosites of those substrates and CEP164 induced by TTBK2 in vitro and in vivo. Intriguingly, we further show that identified TTBK2 phosphosites and consensus sequence delineated from those are distinct from motifs previously assigned to TTBK2. Finally, we show that TTBK2 is also required for efficient phosphorylation of many S/T sites in CEP164 and provide evidence that TTBK2-induced phosphorylations of CEP164 modulate its function, which in turn seems relevant for the process of cilia formation. In summary, our work provides important insight into the substrates-TTBK2 kinase relationship and suggests that phosphorylation of substrates on multiple sites by TTBK2 is probably involved in the control of ciliogenesis in human cells.

Návaznosti

GA19-05244S, projekt VaV

Název: Molekulární aspekty ciliogeneze: zaměření na Tau Tubulin Kinázu 2

Investor: Grantová agentura ČR, Molekulární aspekty ciliogeneze: zaměření na Tau Tubulin Kinázu 2

GJ16-03269Y, projekt VaV

Název: Tau tubulin kináza 2 v ciliogenezi: molekulární mechanismy a funkční důsledky

Investor: Grantová agentura ČR, Tau tubulin kináza 2 v ciliogenezi: molekularní mechanismy a funkční důsledky

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

ROZV/28/LF21/2020, interní kód MU

Název: WnUí3-kateninová dráha a ciliogeneze

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Wnt/β-kateninová dráha a ciliogeneze, Interní rozvojové projekty

90127, velká výzkumná infrastruktura

Název: CIISB II

90129, velká výzkumná infrastruktura

Název: Czech-BioImaging II

Citovat

BERNATÍK, Ondřej, Petra PEJŠKOVÁ, David VYSLOUŽIL, Kateřina HANÁKOVÁ, Zbyněk ZDRÁHAL a Lukáš ČAJÁNEK. Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2. Molecular Biology of the Cell. Bethesda: The American Society for Cell Biology, 2020, roč. 31, č. 10, s. 1032-1046. ISSN 1059-1524. Dostupné z: https://dx.doi.org/10.1091/mbc.E19-06-0334.

@article{1638476,
   author = {Bernatík, Ondřej and Pejšková, Petra and Vysloužil, David and Hanáková, Kateřina and Zdráhal, Zbyněk and Čajánek, Lukáš},
   article_location = {Bethesda},
   article_number = {10},
   doi = {http://dx.doi.org/10.1091/mbc.E19-06-0334},
   keywords = {INTRINSICALLY DISORDERED PROTEIN; PRIMARY CILIA; SUBSTRATE DETERMINANTS; MOTHER CENTRIOLE; EARLY STEPS; TTBK2; DOCKING; ATAXIA; CEP164; MUTATIONS},
   language = {eng},
   issn = {1059-1524},
   journal = {Molecular Biology of the Cell},
   title = {Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2},
   url = {https://www.molbiolcell.org/doi/10.1091/mbc.E19-06-0334},
   volume = {31},
   year = {2020}
}

TY  - JOUR
ID  - 1638476
AU  - Bernatík, Ondřej - Pejšková, Petra - Vysloužil, David - Hanáková, Kateřina - Zdráhal, Zbyněk - Čajánek, Lukáš
PY  - 2020
TI  - Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2
JF  - Molecular Biology of the Cell
VL  - 31
IS  - 10
SP  - 1032-1046
EP  - 1032-1046
PB  - The American Society for Cell Biology
SN  - 10591524
KW  - INTRINSICALLY DISORDERED PROTEIN
KW  - PRIMARY CILIA
KW  - SUBSTRATE DETERMINANTS
KW  - MOTHER CENTRIOLE
KW  - EARLY STEPS
KW  - TTBK2
KW  - DOCKING
KW  - ATAXIA
KW  - CEP164
KW  - MUTATIONS
UR  - https://www.molbiolcell.org/doi/10.1091/mbc.E19-06-0334
L2  - https://www.molbiolcell.org/doi/10.1091/mbc.E19-06-0334
N2  - Primary cilia are organelles necessary for proper implementation of developmental and homeostasis processes. To initiate their assembly, coordinated actions of multiple proteins are needed. Tau tubulin kinase 2 (TTBK2) is a key player in the cilium assembly pathway, controlling the final step of cilia initiation. The function of TTBK2 in ciliogenesis is critically dependent on its kinase activity; however, the precise mechanism of TTBK2 action has so far not been fully understood due to the very limited information about its relevant substrates. In this study, we demonstrate that CEP83, CEP89, CCDC92, Rabin8, and DVL3 are substrates of TTBK2 kinase activity. Further, we characterize a set of phosphosites of those substrates and CEP164 induced by TTBK2 in vitro and in vivo. Intriguingly, we further show that identified TTBK2 phosphosites and consensus sequence delineated from those are distinct from motifs previously assigned to TTBK2. Finally, we show that TTBK2 is also required for efficient phosphorylation of many S/T sites in CEP164 and provide evidence that TTBK2-induced phosphorylations of CEP164 modulate its function, which in turn seems relevant for the process of cilia formation. In summary, our work provides important insight into the substrates-TTBK2 kinase relationship and suggests that phosphorylation of substrates on multiple sites by TTBK2 is probably involved in the control of ciliogenesis in human cells.
ER  -

BERNATÍK, Ondřej, Petra PEJŠKOVÁ, David VYSLOUŽIL, Kateřina HANÁKOVÁ, Zbyněk ZDRÁHAL a Lukáš ČAJÁNEK. Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin Kinase 2. \textit{Molecular Biology of the Cell}. Bethesda: The American Society for Cell Biology, 2020, roč.~31, č.~10, s.~1032-1046. ISSN~1059-1524. Dostupné z: https://dx.doi.org/10.1091/mbc.E19-06-0334.

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