Publication details

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

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Authors

BOSÁKOVÁ Michaela NITĂ Alexandru GREGOR Tomáš VAŘECHA Miroslav GUDERNOVÁ Iva FAFÍLEK Bohumil BÁRTA Tomáš BASHEER Neha POOVAKULATHU ABRAHAM Sara BÁLEK Lukáš TOMANOVÁ Markéta FIALOVÁ KUČEROVÁ Jana BOSÁK Juraj POTĚŠIL David ZIEBA Jennifer SONG Jieun KONIK Peter PARK Sohyun DURAN Ivan ZDRÁHAL Zbyněk ŠMAJS David JANSEN Gert FU Zheng KO Hyuk Wan HAMPL Aleš TRANTÍREK Lukáš KRAKOW Deborah KREJČÍ Pavel

Year of publication 2019
Type Article in Periodical
Magazine / Source Proceedings of the National Academy of Sciences of the United States of America
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.pnas.org/content/pnas/116/10/4316.full.pdf
Doi http://dx.doi.org/10.1073/pnas.1800338116
Keywords fibroblast growth factor; FGFR; intestinal cell kinase; ICK; cilia length
Description 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.
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