ArticleProceedings of the National Academy of Sciences of the United States of America2004
The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Auxilin regulates intestinal stem cell proliferation through EGFR.Stem cell reports · 2022Article
- Volleying plasma membrane proteins from birth to death: Role of J-domain proteins.Frontiers in molecular biosciences · 2022Review
- Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics.International journal of molecular medicine · 2021Article
- Viral journeys on the intracellular highways.Cellular and molecular life sciences : CMLS · 2018Review
- Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae.Rice (New York, N.Y.) · 2017Article
- RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses.British journal of cancer · 2017Article
- From drug response profiling to target addiction scoring in cancer cell models.Disease models & mechanisms · 2015Article
- Selective Inhibitors of Cyclin G Associated Kinase (GAK) as Anti-Hepatitis C Agents.Journal of medicinal chemistry · 2015Article
- AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets.Journal of virology · 2015Article
- Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.PLoS genetics · 2015Article
- Article
- Intratumoral modeling of gefitinib pharmacokinetics and pharmacodynamics in an orthotopic mouse model of glioblastoma.Cancer research · 2013Article
- Induction of autophagy is an early response to gefitinib and a potential therapeutic target in breast cancer.PloS one · 2013Article
- Mitotic moonlighting functions for membrane trafficking proteins.Traffic (Copenhagen, Denmark) · 2011Review
- S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer.World journal of gastroenterology · 2011Article
- Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction.PloS one · 2011Article
- Proteomic analysis of prolactinoma cells by immuno-laser capture microdissection combined with online two-dimensional nano-scale liquid chromatography/mass spectrometry.Proteome science · 2010Article
- Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development.BMC developmental biology · 2010Article
- Epidermal growth factor receptor phosphorylation sites Ser991 and Tyr998 are implicated in the regulation of receptor endocytosis and phosphorylations at Ser1039 and Thr1041.Molecular & cellular proteomics : MCP · 2009Article
- Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice.Molecular biology of the cell · 2008Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Cyclin G-associated kinase (GAK) is a serine/threonine kinase that features high homology outside its kinase domain with auxilin. Like auxilin, GAK has been shown to be a cofactor for uncoating clathrin vesicles in vitro. We investigated epidermal growth factor (EGF) receptor-mediated signaling in cells, in which GAK is down-regulated by small hairpin RNAs. Here, we report that down-regulation of GAK by small hairpin RNA has two pronounced effects on EGF receptor signaling: (i) the levels of receptor expression and tyrosine kinase activity go up by >50-fold; and (ii) the spectrum of downstream signaling is significantly changed. One very obvious result is a large increase in the levels of activated extracellular signal-regulated kinase 5 and Akt. These two effects of GAK down-regulation result from, at least in part, alterations in receptor trafficking, the most striking of which is the persistence of EGF receptor in altered cellular compartment along with activated extracellular signal-regulated kinase 5. The alterations resulting from GAK down-regulation can have distinctive biological consequences: In CV1P cells, down-regulation of GAK results in outgrowth of cells in soft agar, raising the possibility that loss of GAK function may promote tumorigenesis.
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Registered trials
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