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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
The new serine-threonine kinase, Qik, is a target of the Qin oncogene
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC239, La Jolla, California 92037, USA.
Abstract:
The winged helix transcription factor Qin is the avian homolog of the mammalian brain factor 1 (BF-1) and has the potential to act as an oncogenic protein. We used representational difference analysis to identify genes that are differentially expressed in chicken embryo fibroblasts (CEF) transformed by Qin. One of the up-regulated Qin targets identified in this analysis is a serine-threonine kinase termed Qik (Qin-induced kinase). Qik belongs to the AMPK/SNF1 kinase family. It is a ubiquitously expressed protein and is upregulated rapidly after a hormone-regulated form of Qin is activated. In vitro kinase tests demonstrate that Qik is capable of autophosphorylation. Elevated levels of Qik transcripts are also observed in Src-transformed cells, suggesting that Src and Qin share some targets.
Insights
Qin, an avian oncogenic protein, upregulates a serine-threonine kinase called Qin-induced kinase (Qik). Qik is a member of the AMPK/SNF1 kinase family and may be a shared target with Src.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The winged helix transcription factor Qin is an avian homolog of mammalian brain factor 1 (BF-1).
- Qin exhibits oncogenic potential.
- Understanding Qin's downstream targets is crucial for cancer research.
Purpose of the Study:
- To identify genes differentially expressed in chicken embryo fibroblasts (CEF) transformed by Qin.
- To characterize a novel Qin-induced gene, Qik.
- To explore potential shared targets between Qin and Src.
Main Methods:
- Representational difference analysis (RDA) to identify differentially expressed genes.
- In vitro kinase assays to assess Qik activity.
- Analysis of Qik transcript levels in Src-transformed cells.
Main Results:
- Representational difference analysis identified Qik (Qin-induced kinase) as a Qin-upregulated gene.
- Qik is a serine-threonine kinase belonging to the AMPK/SNF1 kinase family.
- Qik is ubiquitously expressed, rapidly upregulated upon Qin activation, and capable of autophosphorylation.
- Elevated Qik transcripts were also found in Src-transformed cells.
Conclusions:
- Qin induces the expression of the serine-threonine kinase Qik.
- Qik is a functional kinase with autophosphorylation activity.
- Qin and Src may share common downstream targets, including Qik.
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