Interaction of a G-protein β-subunit with a conserved sequence in Ste20/PAK family protein kinases

Serine/threonine protein kinases of the Ste20/PAK family have been implicated in the signalling from heterotrimeric G proteins to mitogen-activated protein (MAP) kinase cascades(1,2). in the yeast Saccharomyces cerevisiae, Ste20 is involved in transmitting the mating-pheromone signal from the beta gamma-subunits (encoded by the STE4 and STE18 genes, respectively) of a heterotrimeric G protein to a downstream MAP kinase cascade(1). We have identified a binding site for the G-protein beta-subunit (G beta) in the non-catalytic carboxy-terminal regions of Ste20 and its mammalian homologues, the p21-activated protein kinases (PAKs). Association of G beta with this site in Ste20 was regulated by binding of pheromone to the receptor. Mutations in G beta and Ste20 that prevented this association blocked activation of the MAP kinase cascade. Considering the high degree of structural and functional conservation of Ste20/PAK family members and G-protein subunits, our results provide a possible model for a role of these kinases in G beta gamma-mediated signal transduction in organisms ranging from yeast to mammals.