Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase
| Autor: | Bohumil Fafilek, Peter Konik, Iva Gudernova, Jennifer Zieba, Miroslav Varecha, Sara P. Abraham, Tomas Gregor, Ivan Duran, David Šmajs, Gert Jansen, Marketa Tomanova, Pavel Krejci, So Hyun Park, Jieun Song, Tomáš Bárta, Deborah Krakow, Lukas Balek, Alexandru Nita, David Potesil, Zheng Fu, Neha Basheer, Hyuk Wan Ko, Aleš Hampl, Michaela Bosakova, Jana Kučerová, Juraj Bosák, Lukáš Trantírek, Zbynek Zdrahal |
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| Přispěvatelé: | Cell biology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Proteomics
animal structures Protein Serine-Threonine Kinases Fibroblast growth factor 03 medical and health sciences Mice Ciliogenesis fibroblast growth factor Animals Humans Receptor Fibroblast Growth Factor Type 3 Hedgehog Proteins Protein Interaction Domains and Motifs Receptor Fibroblast Growth Factor Type 4 Cilia Receptor Fibroblast Growth Factor Type 1 Kinase activity Phosphorylation 030304 developmental biology Mice Knockout 0303 health sciences Multidisciplinary Chemistry Kinase FGFR Cilium 030302 biochemistry & molecular biology intestinal cell kinase Cell Biology Biological Sciences ICK Receptors Fibroblast Growth Factor Hedgehog signaling pathway Cell biology Fibroblast Growth Factors Molecular Docking Simulation HEK293 Cells PNAS Plus Fibroblast growth factor receptor cilia length Models Animal NIH 3T3 Cells sense organs CRISPR-Cas Systems Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the U.S.A., 116(10), 4316-4325. National Academy of Sciences |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance A properly functioning primary cilium is prerequisite for both normal development and aging of all ciliated organisms, including humans. In vertebrates, the signaling of Hedgehog family morphogens depends entirely on primary cilium. Recently, we reported that fibroblast growth factors (FGF) signaling interacts with that of Hedgehog, and that this is a consequence of FGF regulating length of the cilium and speed of processes that happen therein. In this report, we provide a molecular mechanism of such interaction, identifying intestinal cell kinase as a mediator of the FGF-induced changes in the ciliary morphology and function. This expands our understanding how FGF signaling regulates intracellular processes, and how aberrant FGF signaling contributes to diseases, such as achondroplasia and cancer. Vertebrate primary cilium is a Hedgehog signaling center but the extent of its involvement in other signaling systems is less well understood. This report delineates a mechanism by which fibroblast growth factor (FGF) controls primary cilia. Employing proteomic approaches to characterize proteins associated with the FGF-receptor, FGFR3, we identified the serine/threonine kinase intestinal cell kinase (ICK) as an FGFR interactor. ICK is involved in ciliogenesis and participates in control of ciliary length. FGF signaling partially abolished ICK’s kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. Activation of the FGF signaling pathway affected both primary cilia length and function in a manner consistent with cilia effects caused by inhibition of ICK activity. Moreover, knockdown and knockout of ICK rescued the FGF-mediated effect on cilia. We provide conclusive evidence that FGF signaling controls cilia via interaction with ICK. |
| Databáze: | OpenAIRE |
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