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;

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 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

Institute of Animal Physiology and Genetics Czech Academy of Sciences 60200 Brno Czech Republic

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

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

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