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Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase
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 as...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410813/ https://www.ncbi.nlm.nih.gov/pubmed/30782830 http://dx.doi.org/10.1073/pnas.1800338116 |
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author | Kunova Bosakova, Michaela Nita, Alexandru Gregor, Tomas Varecha, Miroslav Gudernova, Iva Fafilek, Bohumil Barta, Tomas Basheer, Neha Abraham, Sara P. Balek, Lukas Tomanova, Marketa Fialova Kucerova, Jana Bosak, Juraj Potesil, David Zieba, Jennifer Song, Jieun Konik, Peter Park, Sohyun Duran, Ivan Zdrahal, Zbynek Smajs, David Jansen, Gert Fu, Zheng Ko, Hyuk Wan Hampl, Ales Trantirek, Lukas Krakow, Deborah Krejci, Pavel |
author_facet | Kunova Bosakova, Michaela Nita, Alexandru Gregor, Tomas Varecha, Miroslav Gudernova, Iva Fafilek, Bohumil Barta, Tomas Basheer, Neha Abraham, Sara P. Balek, Lukas Tomanova, Marketa Fialova Kucerova, Jana Bosak, Juraj Potesil, David Zieba, Jennifer Song, Jieun Konik, Peter Park, Sohyun Duran, Ivan Zdrahal, Zbynek Smajs, David Jansen, Gert Fu, Zheng Ko, Hyuk Wan Hampl, Ales Trantirek, Lukas Krakow, Deborah Krejci, Pavel |
author_sort | Kunova Bosakova, Michaela |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6410813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-64108132019-03-13 Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase Kunova Bosakova, Michaela Nita, Alexandru Gregor, Tomas Varecha, Miroslav Gudernova, Iva Fafilek, Bohumil Barta, Tomas Basheer, Neha Abraham, Sara P. Balek, Lukas Tomanova, Marketa Fialova Kucerova, Jana Bosak, Juraj Potesil, David Zieba, Jennifer Song, Jieun Konik, Peter Park, Sohyun Duran, Ivan Zdrahal, Zbynek Smajs, David Jansen, Gert Fu, Zheng Ko, Hyuk Wan Hampl, Ales Trantirek, Lukas Krakow, Deborah Krejci, Pavel Proc Natl Acad Sci U S A PNAS Plus 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. National Academy of Sciences 2019-03-05 2019-02-19 /pmc/articles/PMC6410813/ /pubmed/30782830 http://dx.doi.org/10.1073/pnas.1800338116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | PNAS Plus Kunova Bosakova, Michaela Nita, Alexandru Gregor, Tomas Varecha, Miroslav Gudernova, Iva Fafilek, Bohumil Barta, Tomas Basheer, Neha Abraham, Sara P. Balek, Lukas Tomanova, Marketa Fialova Kucerova, Jana Bosak, Juraj Potesil, David Zieba, Jennifer Song, Jieun Konik, Peter Park, Sohyun Duran, Ivan Zdrahal, Zbynek Smajs, David Jansen, Gert Fu, Zheng Ko, Hyuk Wan Hampl, Ales Trantirek, Lukas Krakow, Deborah Krejci, Pavel Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase |
title | Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase |
title_full | Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase |
title_fullStr | Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase |
title_full_unstemmed | Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase |
title_short | Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase |
title_sort | fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410813/ https://www.ncbi.nlm.nih.gov/pubmed/30782830 http://dx.doi.org/10.1073/pnas.1800338116 |
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