NOVEL FORM OF CROSSTALK BETWEEN G-PROTEIN AND TYROSINE KINASE PATHWAYS

Neuronal Ca2+ channels are inhibited by a variety of transmitter recep tors coupled to G(o)-type GTP-binding proteins. G(o) has been postulat ed to work via a direct interaction between an activated G protein sub unit and the Ca2+ channel complex. Here we show that the inhibition of sensory neuron N-type Ca2+ channels produced by gamma-aminobutyric ac id involves a novel, rapidly activating tyrosine kinase signaling path way that is mediated by G alpha(o), and a src-like kinase. In contrast to other recently described G protein-coupled tyrosine kinase pathway s, the G alpha(o)-mediated modulation requires neither protein kinase C nor intracellular Ca2+. The results suggest that this pathway mediat es rapid receptor-G protein signaling in the nervous system and suppor t the existence of a previously unrecognized form of crosstalk between G protein and tyrosine kinase pathways.