Novel form of crosstalk between G protein and tyrosine kinase pathways.
Neuronal Ca2+ channels are inhibited by a variety of transmitter receptors coupled to Go-type GTP-binding proteins. Go has been postulated to work via a direct interaction between an activated G protein subunit and the Ca2+ channel complex. Here we show that the inhibition of sensory neuron N-type Ca2+ channels produced by gamma-aminobutyric acid involves a novel, rapidly activating tyrosine kinase signaling pathway that is mediated by Galphao and a src-like kinase. In contrast to other recently described G protein-coupled tyrosine kinase pathways, the Galphao-mediated modulation requires neither protein kinase C nor intracellular Ca2+. The results suggest that this pathway mediates rapid receptor-G protein signaling in the nervous system and support the existence of a previously unrecognized form of crosstalk between G protein and tyrosine kinase pathways.
Diversé-Pierluissi
M
M
Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Remmers
A E
AE
Neubig
R R
RR
Dunlap
K
K
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D018411:Spodoptera; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D015220:Calcium Channels; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D005680:gamma-Aminobutyric Acid; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins