Second messenger and Ras/MAPK signalling pathways regulate CLOCK/CYCLE-dependent transcription
| Autor: | Hsiu-Cheng Hung, Steve A. Kay, Christian Maurer, Frank Weber |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
MAPK/ERK pathway
Transcription Genetic Circadian clock CLOCK Proteins Gene Expression Models Biological Biochemistry Cellular and Molecular Neuroscience Genes Reporter Basic Helix-Loop-Helix Transcription Factors Animals Drosophila Proteins Calcium Signaling Enzyme Inhibitors Phosphorylation Luciferases Protein kinase A CAMK Dose-Response Relationship Drug biology Kinase ARNTL Transcription Factors Gene Expression Regulation Mitogen-activated protein kinase biology.protein Drosophila Signal Transduction Transcription Factors |
| Zdroj: | Journal of Neurochemistry. 98:248-257 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/j.1471-4159.2006.03865.x |
| Popis: | The heterodimeric complex of the transcription factors CLOCK (CLK) and CYCLE (CYC) constitutes the positive element of the circadian clock in Drosophila and mammals. Phosphorylation of clock proteins represents an essential mechanism for promotion and control of the molecular oscillator. However, the kinases and signalling pathways that regulate CLK/CYC function remain largely elusive. In the present study we performed a chemical screen of kinase inhibitors in a cell culture reporter assay to identify functional regulators of CLK/CYC-dependent gene expression. These studies and analysis of constitutively active forms of kinases revealed that cyclic nucleotide/protein kinase A (PKA), calcium/calmodulin-dependent kinase (CaMK) II and Ras/mitogen-activated protein kinase (MAPK) regulate CLK/CYC activity. In vitro phosphorylation analysis showed a direct phosphorylation of CLK by CaMK II and p42 MAPK [extracellular signal-regulated kinase (ERK) 2], suggesting that these kinases regulate CLK/CYC-dependent transcription by direct phosphorylation of CLK. |
| Databáze: | OpenAIRE |
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