Receptor tyrosine kinase transactivation: fine-tuning synaptic transmission

Trends Neurosci. 2003 Mar;26(3):119-22. doi: 10.1016/S0166-2236(03)00022-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Brain / metabolism*
  • Cognition Disorders / metabolism
  • Dopamine / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D4
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction
  • Synaptic Transmission*

Substances

  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Dopamine D4
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor beta
  • Mitogen-Activated Protein Kinases
  • Dopamine