Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase

Michaela Kunova Bosakova, Alexandru Nita, Tomas Gregor, Miroslav Varecha, Iva Gudernova, Bohumil Fafilek, Tomas Barta, Neha Basheer, Sara P. Abraham, Lukas Balek, Marketa Tomanova, Jana Fialova Kucerova, Juraj Bosak, David Potesil, Jennifer Zieba, Jieun Song, Peter Konik, Sohyun Park, Ivan Duran, Zbynek ZdrahalDavid Smajs, Gert Jansen, Zheng Fu, Hyuk Wan Ko, Ales Hampl, Lukas Trantirek, Deborah Krakow, Pavel Krejci

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3 Citations (Scopus)

Abstract

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 pro-teomic 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.

Original languageEnglish
Pages (from-to)4316-4325
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number10
DOIs
Publication statusPublished - 2019

All Science Journal Classification (ASJC) codes

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    Bosakova, M. K., Nita, A., Gregor, T., Varecha, M., Gudernova, I., Fafilek, B., Barta, T., Basheer, N., Abraham, S. P., Balek, L., Tomanova, M., Kucerova, J. F., Bosak, J., Potesil, D., Zieba, J., Song, J., Konik, P., Park, S., Duran, I., ... Krejci, P. (2019). Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase. Proceedings of the National Academy of Sciences of the United States of America, 116(10), 4316-4325. https://doi.org/10.1073/pnas.1800338116