Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase.
Animals
CRISPR-Cas Systems
Cilia
/ metabolism
Fibroblast Growth Factors
/ metabolism
HEK293 Cells
Hedgehog Proteins
/ metabolism
Humans
Mice
Mice, Knockout
Models, Animal
Molecular Docking Simulation
NIH 3T3 Cells
Phosphorylation
Protein Interaction Domains and Motifs
Protein Serine-Threonine Kinases
/ genetics
Proteomics
Receptor, Fibroblast Growth Factor, Type 1
/ metabolism
Receptor, Fibroblast Growth Factor, Type 3
/ genetics
Receptor, Fibroblast Growth Factor, Type 4
/ metabolism
Receptors, Fibroblast Growth Factor
/ genetics
Signal Transduction
FGFR
ICK
cilia length
fibroblast growth factor
intestinal cell kinase
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 03 2019
05 03 2019
Historique:
pubmed:
21
2
2019
medline:
24
3
2020
entrez:
21
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30782830
pii: 1800338116
doi: 10.1073/pnas.1800338116
pmc: PMC6410813
doi:
Substances chimiques
Hedgehog Proteins
0
Receptors, Fibroblast Growth Factor
0
Fibroblast Growth Factors
62031-54-3
CILK1 protein, human
EC 2.7.1.-
FGFR1 protein, human
EC 2.7.10.1
FGFR3 protein, human
EC 2.7.10.1
FGFR4 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 1
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 3
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 4
EC 2.7.10.1
Cilk1 protein, mouse
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4316-4325Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE019567
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000124
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA195273
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127690
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR066124
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR062651
Pays : United States
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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