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 Zdrahal; David Smajs; Gert Jansen; Zheng Fu; Hyuk Wan Ko; Ales Hampl; Lukas Trantirek; Deborah Krakow; Pavel Krejci

doi:10.1073/pnas.1800338116

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

Department of Biochemistry

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23 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 language	English
Pages (from-to)	4316-4325
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	116
Issue number	10
DOIs	https://doi.org/10.1073/pnas.1800338116
Publication status	Published - 2019

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© 2018 National Academy of Sciences. All Rights Reserved.

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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

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title = "Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase",

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{\textquoteright}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.",

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

year = "2019",

doi = "10.1073/pnas.1800338116",

language = "English",

volume = "116",

pages = "4316--4325",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "10",

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Bosakova, MK, Nita, A, Gregor, T, Varecha, M, Gudernova, I, Fafilek, B, Barta, T, Basheer, N, Abraham, SP, Balek, L, Tomanova, M, Kucerova, JF, Bosak, J, Potesil, D, Zieba, J, Song, J, Konik, P, Park, S, Duran, I, Zdrahal, Z, Smajs, D, Jansen, G, Fu, Z, Ko, HW, Hampl, A, Trantirek, L, Krakow, D & 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, vol. 116, no. 10, pp. 4316-4325. https://doi.org/10.1073/pnas.1800338116

Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase. / Bosakova, Michaela Kunova; Nita, Alexandru; Gregor, Tomas et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 10, 2019, p. 4316-4325.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase

AU - Bosakova, Michaela Kunova

AU - Nita, Alexandru

AU - Gregor, Tomas

AU - Varecha, Miroslav

AU - Gudernova, Iva

AU - Fafilek, Bohumil

AU - Barta, Tomas

AU - Basheer, Neha

AU - Abraham, Sara P.

AU - Balek, Lukas

AU - Tomanova, Marketa

AU - Kucerova, Jana Fialova

AU - Bosak, Juraj

AU - Potesil, David

AU - Zieba, Jennifer

AU - Song, Jieun

AU - Konik, Peter

AU - Park, Sohyun

AU - Duran, Ivan

AU - Zdrahal, Zbynek

AU - Smajs, David

AU - Jansen, Gert

AU - Fu, Zheng

AU - Ko, Hyuk Wan

AU - Hampl, Ales

AU - Trantirek, Lukas

AU - Krakow, Deborah

AU - Krejci, Pavel

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

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U2 - 10.1073/pnas.1800338116

DO - 10.1073/pnas.1800338116

M3 - Article

C2 - 30782830

AN - SCOPUS:85062661279

SN - 0027-8424

VL - 116

SP - 4316

EP - 4325

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 10

ER -

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

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