Abstract
Many neurodegenerative diseases, such as Parkinson's disease, can be directly correlated with the deregulation in neuronal signaling. Hence, it is indispensable for therapy development to understand the participating signaling processes. Because the activity of the involved protein kinases is of major interest for the investigation of these signaling processes, an affinity-based chemical proteomics approach that allows for the activity profiling of protein kinases was developed within this study. This approach was applied to investigate the RET9 receptor tyrosine kinase signaling pathway that plays a central role in neuronal signaling. In addition to already known RET9 downstream targets, several other protein kinases were found to be highly activated upon RET9 stimulation.
MeSH terms
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Animals
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Blotting, Western
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Cell Line, Tumor
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Chromatography, Liquid
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Gene Expression Profiling
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Humans
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Imidazoles / chemistry
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Imidazoles / metabolism
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Models, Molecular
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Molecular Structure
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Neurodegenerative Diseases / metabolism*
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Neurons / physiology*
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Protein Binding
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Protein Kinases / metabolism*
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Proteomics / methods*
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Proto-Oncogene Proteins c-ret / metabolism*
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Pyrimidines / chemistry
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Pyrimidines / metabolism
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Rats
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Signal Transduction / genetics
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Signal Transduction / physiology*
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Tandem Mass Spectrometry
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Imidazoles
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Pyrimidines
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SB 218655
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Protein Kinases
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Proto-Oncogene Proteins c-ret
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RET protein, human
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p38 Mitogen-Activated Protein Kinases