A conserved G(beta) binding (GBB) sequence motif in Ste20p/PAK family protein kinases

Serine/threonine protein kinases of the Ste20p/PAK family are highly conser ved from yeast to man. These protein kinases have been implicated in the si gnaling from heterotrimeric G proteins to mitogen-activated protein (MAP) k inase cascades and to cytoskeletal components such as myosin-I. In the yeas t Saccharomyces cerevisiae, Ste20p is involved in transmitting the mating-p heromone signal from the beta gamma-subunits of a heterotrimeric G protein to a downstream MAP kinase cascade. We have previously shown that binding o f the G-protein beta-subunit (G(beta)) to a short binding site in the non-c atalytic carboxy-terminal region of Ste20p is essential for transmitting th e pheromone signal. In this study, we searched protein sequence databases f or sequences that are similar to the G(beta) binding site in Ste20p. We ide ntified a sequence motif with the consensus sequence SSL phi PLI/Vx phi phi beta (x: any residue; phi: A,I,L,S, or T; beta: basic residues) that is so lely present in members of Ste20p/PAK family protein kinases. We propose th at this sequence motif, which we have designated GBB (G(beta) binding) moti f, is specifically responsible for binding of G(beta) to Ste20p/PAK protein kinases in response to activation of heterotrimeric G protein coupled rece ptors. Thus, the GBB motif is a novel type of signaling domain that serves to link protein kinases of the Ste20p/PAK family to G protein coupled recep tors.