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

Abstract：

: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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

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

doi

10.1073/pnas.1800338116

subject

Has Abstract

pub_date

2019-03-05 00:00:00

pages

4316-4325

issue

10

eissn

0027-8424

issn

1091-6490

pii

1800338116

journal_volume

116

pub_type

杂志文章

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