Structural Analysis of Hippocampal Kinase Signal Transduction
| Autor: | Mathieu Lavalle-Adam, Nam-Kyung Yu, Salvador Martínez-Bartolomé, John R. Yates, Daniel B. McClatchy, Alexander R. Pelletier, Reesha R. Patel, Susan B. Powell, Marissa Roberto |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Potassium Channels Physiology MAP Kinase Signaling System Cognitive Neuroscience Hippocampal formation Biochemistry Hippocampus Mass Spectrometry Article Protein–protein interaction Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine In vivo Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Animals Immunoprecipitation Protein Interaction Maps Protein kinase B Gene Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Chemistry Kinase Cell Biology General Medicine Cell biology Rats 030104 developmental biology Signal transduction Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Function (biology) Signal Transduction |
| Zdroj: | ACS chemical neuroscience. 9(12) |
| ISSN: | 1948-7193 |
| Popis: | Kinases are a major clinical target for human diseases. Identifying the proteins that interact with kinases in vivo will provide information on unreported substrates and will potentially lead to more specific methods for therapeutic kinase regulation. Here, endogenous immunoprecipitations of evolutionally distinct kinases (i.e., Akt, ERK2, and CAMK2) from rodent hippocampi were analyzed by mass spectrometry to generate three highly confident kinase protein-protein interaction networks. Proteins of similar function were identified in the networks, suggesting a universal model for kinase signaling complexes. Protein interactions were observed between kinases with reported symbiotic relationships. The kinase networks were significantly enriched in genes associated with specific neurodevelopmental disorders providing novel structural connections between these disease-associated genes. To demonstrate a functional relationship between the kinases and the network, pharmacological manipulation of Akt in hippocampal slices was shown to regulate the activity of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel(HCN1), which was identified in the Akt network. Overall, the kinase protein-protein interaction networks provide molecular insight of the spatial complexity of in vivo kinase signal transduction which is required to achieve the therapeutic potential of kinase manipulation in the brain. |
| Databáze: | OpenAIRE |
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