Receptor tyrosine kinase transactivation: fine-tuning synaptic transmission.
G-protein-coupled receptors generate signals that promote gene transcription through the 'transactivation' of receptor tyrosine kinases (RTKs) and activation of the mitogen-activated protein kinase (MAPK) cascade -- a process that involves RTK autophosphorylation and endocytosis. Pioneering work now suggests that D4-dopamine-receptor-mediated transactivation of the platelet-derived growth factor beta receptor has immediate effects on synaptic neurotransmission via Ca(2+)-dependent inactivation of NMDA receptors. The demonstration of a physiological role for RTK transactivation in the CNS provides novel opportunities for understanding how aberrant dopamine signalling might contribute to cognitive and attention deficits associated with schizophrenia and attention-deficit hyperactivity disorder.
Ferguson
Stephen S G
SS
Cell Biology Research Group, Robarts Research Institute, Department of Physiology and Pharmacology, University of Western Ontario, 100 Perth Drive, PO Box 5015, London, Ontario, Canada N6A 5K8. ferguson@robarts.ca
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission
D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D050638:Receptors, Dopamine D4; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine