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.

• Keywords
• FGFR, ICK, cilia length, fibroblast growth factor, intestinal cell kinase,
• MeSH
• NIH 3T3 Cells MeSH
• Cilia metabolism   MeSH
• CRISPR-Cas Systems MeSH
• Fibroblast Growth Factors metabolism   MeSH
• Phosphorylation MeSH
• HEK293 Cells MeSH
• Protein Interaction Domains and Motifs MeSH
• Humans MeSH
• Models, Animal MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Protein Serine-Threonine Kinases genetics   metabolism   MeSH
• Hedgehog Proteins metabolism   MeSH
• Proteomics MeSH
• Receptor, Fibroblast Growth Factor, Type 1 metabolism   MeSH
• Receptor, Fibroblast Growth Factor, Type 3 genetics   metabolism   MeSH
• Receptor, Fibroblast Growth Factor, Type 4 metabolism   MeSH
• Receptors, Fibroblast Growth Factor genetics   metabolism   MeSH
• Signal Transduction MeSH
• Molecular Docking Simulation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• CILK1 protein, human MeSH Browser
• Cilk1 protein, mouse MeSH Browser
• FGFR1 protein, human MeSH Browser
• FGFR3 protein, human MeSH Browser
• FGFR4 protein, human MeSH Browser
• Fibroblast Growth Factors MeSH
• Protein Serine-Threonine Kinases MeSH
• Hedgehog Proteins MeSH
• Receptor, Fibroblast Growth Factor, Type 1 MeSH
• Receptor, Fibroblast Growth Factor, Type 3 MeSH
• Receptor, Fibroblast Growth Factor, Type 4 MeSH
• Receptors, Fibroblast Growth Factor MeSH