cAMP cascade leads to Ras activation in cortical neurons
| Autor: | Silvia Tininini, Renata Zippel, Anna Barassi, Giorgio Racagni, A. Ambrosini, Emmapaola Sturani |
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| Rok vydání: | 2000 |
| Předmět: |
MAPK/ERK pathway
Biology PC12 Cells Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Fetus Anti-apoptotic Ras signalling cascade Cyclic AMP Animals Protein kinase A Molecular Biology Phorbol 12 13-Dibutyrate Protein kinase C G protein-coupled receptor Cerebral Cortex Mitogen-Activated Protein Kinase 1 Neurons Mice Inbred ICR Mitogen-Activated Protein Kinase 3 Forskolin Kinase Colforsin Molecular biology Rats Cell biology Enzyme Activation chemistry ras GTPase-Activating Proteins ras Proteins cAMP-dependent pathway Guanosine Triphosphate Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | Molecular Brain Research. 75:54-60 |
| ISSN: | 0169-328X |
| DOI: | 10.1016/s0169-328x(99)00294-6 |
| Popis: | Monoaminergic G protein-coupled receptors (GPCRs) are highly expressed in the CNS at the cerebrocortical level, where they support a variety of behavioural responses. To elucidate possible intracellular signalling pathways coupled to these receptors, we have studied their ability to activate extracellular signal-regulated kinases (ERKs) in cultured cortical neurons. An increase in ERK activity was observed after stimulation of neurons with dopamine or serotonin, and with agonists selective for various GPCRs. In addition, ERK activation was also observed following treatment with phorbol dibutyrate (PdBu) and forskolin, activators of protein kinase C (PKC) and protein kinase A (PKA), respectively. Concomitant with ERK activation, all the monoaminergic agonists tested also increased the level of active Ras (Ras-GTP). Surprisingly, Ras activation was also observed after activation of cAMP pathway, and this effect was at least in part mediated by PKA. Ras activation by cAMP was unique for neurons, since in PC12 cells forskolin caused activation of ERK but did not increase Ras-GTP level. These results highlight the relevance of Ras as a target for multiple signalling cascades leading to activation of the ERK pathway in neurons. |
| Databáze: | OpenAIRE |
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