ArticleProceedings of the National Academy of Sciences of the United States of America2014
Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 92 citations in OpenAlex.
- Structure Makes a Difference: IFT Complex in Ciliary Function and Ciliopathy.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Imbalance of Ciliary Programs Drives Fibroblast Differentiation and Fibrotic Signaling in Systemic Sclerosis.bioRxiv : the preprint server for biology · 2026Article
- Progressive tooth pattern changes in Cilk1-deficient mice depending on Hedgehog signaling.International journal of oral science · 2025Article
- Article
- Human disease variants of KATNIP fail to support CILK1 activation and control of primary cilia.Journal of cell science · 2025Article
- A homozygous frameshift variant in the CILK1 gene causes cranioectodermal dysplasia.European journal of human genetics : EJHG · 2025Article
- Genetic Animal Models of Idiopathic Generalized Epilepsies: What Can We Learn from Them?Biomedicines · 2025Review
- Kinase-dependent regulation of ciliary protein transport and its implications for therapy.Frontiers in molecular biosciences · 2025Review
- Distinct roles of centriole distal appendage proteins in ciliary assembly and disassembly.Cell communication and signaling : CCS · 2024Article
- The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?Biomedicines · 2024Review
- Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival.Life science alliance · 2024Article
- Article
- Positive regulation of Hedgehog signaling via phosphorylation of GLI2/GLI3 by DYRK2 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- An epilepsy-associated CILK1 variant compromises KATNIP regulation and impairs primary cilia and Hedgehog signaling.bioRxiv : the preprint server for biology · 2024Article
- Skeletal ciliopathy: pathogenesis and related signaling pathways.Molecular and cellular biochemistry · 2024Review
- Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1.International journal of biological sciences · 2024Article
- Illumination of understudied ciliary kinases.Frontiers in molecular biosciences · 2024Review
- CMGC Kinases in Health and Cancer.Cancers · 2023Review
- The Scaffold Protein KATNIP Enhances CILK1 Control of Primary Cilia.Molecular and cellular biology · 2023Article
- BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1.Molecular biology of the cell · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder associated with multiple congenital defects in endocrine, cerebral, and skeletal systems that is caused by a missense mutation in the mitogen-activated protein kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK homologs are involved in flagellar formation and ciliogenesis, respectively. However, it is not clear whether this role of ICK is conserved in mammals and how a lack of functional ICK results in the characteristic phenotypes of human ECO syndrome. Here, we generated Ick knockout mice to elucidate the precise role of ICK in mammalian development and to examine the pathological mechanisms of ECO syndrome. Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes. In cultured cells, down-regulation of Ick or overexpression of kinase-dead or ECO syndrome mutant ICK resulted in an elongation of primary cilia and abnormal Sonic hedgehog (Shh) signaling. Wild-type ICK proteins were generally localized in the proximal region of cilia near the basal bodies, whereas kinase-dead ICK mutant proteins accumulated in the distal part of bulged ciliary tips. Consistent with these observations in cultured cells, Ick knockout mouse embryos displayed elongated cilia and reduced Shh signaling during limb digit patterning. Taken together, these results indicate that ICK plays a crucial role in controlling ciliary length and that ciliary defects caused by a lack of functional ICK leads to abnormal Shh signaling, resulting in congenital disorders such as ECO syndrome.
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