MITOGEN-ACTIVATED protein kinases, MAP kinases or ERKs (extracellular
signal-regulated kinases) are rapidly stimulated by growth-promoting f
actors acting on a variety of cell-surface receptors (1,2). In turn, E
RKs phosphorylate and regulate key intracellular enzymes and transcrip
tion factors involved in the control of cellular proliferation(3,4). T
he tyrosine-kinase class of growth-factor receptors transmits signals
to ERKs in a multistep process that involves Ras and a limited number
of defined molecules(5). In contrast, ERK activation by G-protein-coup
led receptors is poorly understood(3,6), as is the role of ras in this
signalling pathway(7,8). We have explored in COS-7 cells the mechanis
m of ERKs activation by m1 and m2 muscarinic receptors, typical exampl
es of receptors coupled through Gq proteins to induce phosphatidylinos
itol hydrolysis and to G(i) proteins to inhibit adenylyl cyclase, resp
ectively(9). Here we present evidence that ERK activation is mediated
by beta gamma subunits of heterotrimeric G proteins acting on a ras-de
pendent pathway.