ArticlePloS one2011
Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- In-cell proximity target validation methods for heterobifunctional molecules with CRBN- or VHL-binder using AirID.Communications biology · 2025Article
- BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals.Antiviral research · 2020Article
- Dlx1/2 mice have abnormal enteric nervous system function.JCI insight · 2020Article
- SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK).Journal of medicinal chemistry · 2019Article
- Whole genome sequencing to identify predictive markers for the risk of drug-induced interstitial lung disease.PloS one · 2019Article
- Chemical genetic identification of GAK substrates reveals its role in regulating NaLife science alliance · 2018Article
- Structural Basis for the Inhibition of Cyclin G-Associated Kinase by Gefitinib.ChemistryOpen · 2018Article
- Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.Scientific reports · 2018Article
- Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase.ChemMedChem · 2018Article
- GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase.Cell cycle (Georgetown, Tex.) · 2017Article
- Family-wide Structural Analysis of Human Numb-Associated Protein Kinases.Structure (London, England : 1993) · 2016Article
- The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain.Journal of cell science · 2015Article
- Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.PLoS genetics · 2015Article
- Structure of cyclin G-associated kinase (GAK) trapped in different conformations using nanobodies.The Biochemical journal · 2014Article
- Parkinson's disease-implicated kinases in the brain; insights into disease pathogenesis.Frontiers in molecular neuroscience · 2014Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gefitinib (Iressa) is an inhibitor of the epidermal growth factor receptor (EGFR) that has shown promising activity in the treatment of patients with non-small cell lung cancer (NSCLC). However, adverse side effects of gefitinib treatment, such as respiratory dysfunction, have limited the therapeutic benefit of this targeting strategy. The present results show that this adverse effect can be attributed to the inhibition of the novel gefitinib target GAK (Cyclin G-associated kinase), which is as potently inhibited by the drug as the tyrosine kinase activity of EGFR. Knockout mice expressing the kinase-dead form of GAK (GAK-kd) died within 30 min after birth primarily due to respiratory dysfunction. Immunohistochemical analysis revealed that surfactant protein A (SP-A) was abundant within alveolar spaces in GAK-kd(+/+) mice but not in GAK-kd(-/-) pups. E-cadherin and phosphorylated EGFR signals were also abnormal, suggesting the presence of flat alveolar cells with thin junctions. These results suggest that inhibition of GAK by gefitinib may cause pulmonary alveolar dysfunction, and the present study may help prevent side effects associated with gefitinib therapy in NSCLC patients.
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