Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin kinase 2
| Autor: | Zbynek Zdrahal, David Vyslouzil, Ondrej Bernatik, Katerina Hanakova, Petra Pejskova, Lukas Cajanek |
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| Rok vydání: | 2020 |
| Předmět: |
Cell Physiology
Organogenesis Amino Acid Motifs Protein Serine-Threonine Kinases Biology Substrate Specificity Phosphoserine 03 medical and health sciences 0302 clinical medicine Ciliogenesis CEP164 Humans Cilia Phosphorylation Kinase activity Molecular Biology 030304 developmental biology 0303 health sciences Chemistry Casein Kinase I Kinase Cilium Articles Cell Biology Tau tubulin kinase 2 Cilium assembly Cell biology HEK293 Cells Phosphothreonine Multiprotein Complexes 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Primary cilia (PC) 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 final step of cilia initiation. The function of TTBK2 in ciliogenesisis is critically dependent on its kinase activity, however, precise mechanism of TTBK2 action is so far incompletely understood, due to very limited information about its relevant substrates. In this study we identify CEP83, CEP89, CCDC92, Rabin8 and DVL3 as substrates of TTBK2 kinase activity. Further, we characterise a set of phosphosites of the newly identified substrates and CEP164, induced by TTBK2in vitroandin 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 address functional relevance of selected phosphorylations of CEP164 and provide evidence that the examined TTBK2-induced phosphorylations of CEP164 are relevant for the process of cilia formation. In summary, our work provides important insight into 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. |
| Databáze: | OpenAIRE |
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