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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11 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

Bibliographical note

Funding Information:
We thank Mikael Altun and Johan Boström for providing the U6 vector. This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic (Grant KONTAKT II LH15231, National Program of Sustainability II Projects LQ1605 and LQ1601); the Agency for Healthcare Research of the Czech Republic (Grants 15-33232A, 15-34405A, and NV18-08-00567); and the Czech Science Foundation (Grants GA17-09525S, 14-31540S, and GJ16-24004Y). D.K. is supported by NIH Grants R01AR062651, R01AR066124, and R01DE019567, and by NIH/National Center for Advancing Translational Science University of California, Los Angeles Clinical and Translational Science Institute Grant UL1TR000124. Z.F. is supported by NIH Grant NIH-GM127690. H.W.K. is supported by Korea Mouse Phenotyping Project NRF2014M3A9D5A01073969 of the Ministry of Science, Information, and Communication Technology and Future Planning through the National Research Foundation. Czech Infrastructure for Integrative Structural Biology Research Infrastructure Project LM2015043 funded by the Ministery of Education, Youth and Sports of the Czech Republic is gratefully acknowledged for the financial support of the measurements at the CEITEC Proteomics Core Facility. M.K.B. was supported by the funds from Masaryk University (Grant MUNI/E/0563/2018). M.K.B. and B.F. are supported by a Junior Researcher award from the Faculty of Medicine, Masaryk University.

Funding Information:
ACKNOWLEDGMENTS. We thank Mikael Altun and Johan Boström for providing the U6 vector. This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic (Grant KONTAKT II LH15231, National Program of Sustainability II Projects LQ1605 and LQ1601); the Agency for Healthcare Research of the Czech Republic (Grants 15-33232A, 15-34405A, and NV18-08-00567); and the Czech Science Foundation (Grants GA17-09525S, 14-31540S, and GJ16-24004Y). D.K. is supported by NIH Grants R01AR062651, R01AR066124, and R01DE019567, and by NIH/National Center for Advancing Translational Science University of California, Los Angeles Clinical and Translational Science Institute Grant UL1TR000124. Z.F. is supported by NIH Grant NIH-GM127690. H.W.K. is supported by Korea Mouse Phenotyping Project NRF2014M3A9D5A01073969 of the Ministry of Science, Information, and Communication Technology and Future Planning through the National Research Foundation. Czech Infrastructure for Integrative Structural Biology Research Infrastructure Project LM2015043 funded by the Ministery of Education, Youth and Sports of the Czech Republic is gratefully acknowledged for the financial support of the measurements at the CEITEC Proteomics Core Facility. M.K.B. was supported by the funds from Masaryk University (Grant MUNI/E/0563/2018). M.K.B. and B.F. are supported by a Junior Researcher award from the Faculty of Medicine, Masaryk University.

Publisher Copyright:
© 2018 National Academy of Sciences. All Rights Reserved.

All Science Journal Classification (ASJC) codes

  • General

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