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

M. Kunova Bosakova, A. Nita, T. Gregor, M. Varecha, I. Gudernova, B. Fafilek, T. Barta, N. Basheer, SP. Abraham, L. Balek, M. Tomanova, J. Fialova Kucerova, J. Bosak, D. Potesil, J. Zieba, J. Song, P. Konik, S. Park, I. Duran, Z. Zdrahal, D....

. 2019 ; 116 (10) : 4316-4325. [pub] 20190219

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20006588

Grantová podpora
R01 DE019567 NIDCR NIH HHS - United States
UL1 TR000124 NCATS NIH HHS - United States
R21 CA195273 NCI NIH HHS - United States
R01 GM127690 NIGMS NIH HHS - United States
R01 AR066124 NIAMS NIH HHS - United States
R01 AR062651 NIAMS NIH HHS - United States
NV15-33232A MZ0 CEP - Centrální evidence projektů
NV15-34405A MZ0 CEP - Centrální evidence projektů

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.

Central European Institute of Technology Masaryk University 62500 Brno Czech Republic

Department of Biochemistry College of Life Science and Biotechnology Yonsei University 03722 Seoul Korea

Department of Biology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Department of Biology Faculty of Medicine Masaryk University 62500 Brno Czech Republic International Clinical Research Center St Anne's University Hospital 65691 Brno Czech Republic

Department of Cell Biology Erasmus Medical Center 3000 CA Rotterdam The Netherlands

Department of Histology and Embryology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Department of Orthopaedic Surgery David Geffen School of Medicine University of California Los Angeles CA 90095

Department of Pharmacology University of Virginia School of Medicine Charlottesville VA 22908

Human Genetics David Geffen School of Medicine University of California Los Angeles CA 90095 Obstetrics and Gynecology David Geffen School of Medicine University of California Los Angeles CA 90095

Institute of Chemistry and Biochemistry Faculty of Science University of South Bohemia 37005 Ceske Budejovice Czech Republic

International Clinical Research Center St Anne's University Hospital 65691 Brno Czech Republic Department of Histology and Embryology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

International Clinical Research Center St Anne's University Hospital 65691 Brno Czech Republic Institute of Animal Physiology and Genetics Czech Academy of Sciences 60200 Brno Czech Republic

Citace poskytuje Crossref.org

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