Happyhour, a Ste20 Family Kinase, Implicates EGFR Signaling in Ethanol-Induced Behaviors
| Autor: | Ulrike Heberlein, Ammon B. Corl, Jeffrey A. Simms, Galit Ophir-Shohat, Julie Gesch, Selena E. Bartlett, Karen H. Berger |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Dopamine Mutant HUMDISEASE Biology Pharmacology Protein Serine-Threonine Kinases MOLNEURO General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Mice Epidermal growth factor Animals Drosophila Proteins Insulin Phosphorylation Receptor Gene Crosses Genetic 060100 BIOCHEMISTRY AND CELL BIOLOGY Ethanol Kinase Biochemistry Genetics and Molecular Biology(all) Cell biology Alcohol-Induced Disorders ErbB Receptors Disease Models Animal Drosophila melanogaster chemistry SIGNALING Mutation Female Signal transduction Genetic screen Signal Transduction |
| Zdroj: | Cell |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2009.03.020 |
| Popis: | SummaryThe consequences of alcohol use disorders (AUDs) are devastating to individuals and society, yet few treatments are currently available. To identify genes regulating the behavioral effects of ethanol, we conducted a genetic screen in Drosophila and identified a mutant, happyhour (hppy), due to its increased resistance to the sedative effects of ethanol. Hppy protein shows strong homology to mammalian Ste20 family kinases of the GCK-1 subfamily. Genetic and biochemical experiments revealed that the epidermal growth factor (EGF)-signaling pathway regulates ethanol sensitivity in Drosophila and that Hppy functions as an inhibitor of the pathway. Acute pharmacological inhibition of the EGF receptor (EGFR) in adult animals altered acute ethanol sensitivity in both flies and mice and reduced ethanol consumption in a preclinical rat model of alcoholism. Inhibitors of the EGFR or components of its signaling pathway are thus potential pharmacotherapies for AUDs. |
| Databáze: | OpenAIRE |
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