Novel form of crosstalk between G protein and tyrosine kinase pathways

Neuronal Ca(2+) channels are inhibited by a variety of transmitter receptors coupled to G(o)-type GTP-binding proteins. G(o) has been postulated to work via a direct interaction between an activated G protein subunit and the Ca(2+) channel complex. Here we show that the inhibition of sensory neuron N-type Ca(2+) channels produced by γ-aminobutyric acid involves a novel, rapidly activating tyrosine kinase signaling pathway that is mediated by Gα(o) and a src-like kinase. In contrast to other recently described G protein-coupled tyrosine kinase pathways, the Gα(o)-mediated modulation requires neither protein kinase C nor intracellular Ca(2+). 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.