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

Author

Listed:
  • Thomas Leeuw

    (Eukaryotic Genetics Group, National Research Council of Canada)

  • Cunle Wu

    (Eukaryotic Genetics Group, National Research Council of Canada)

  • Joseph D. Schrag

    (Macromolecular Structure Group, Biotechnology Research Institute, National Research Council of Canada)

  • Malcolm Whiteway

    (Eukaryotic Genetics Group, National Research Council of Canada
    McGill University)

  • David Y. Thomas

    (Eukaryotic Genetics Group, National Research Council of Canada
    McGill University
    McGill University)

  • Ekkehard Leberer

    (Eukaryotic Genetics Group, National Research Council of Canada
    McGill University)

Abstract

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 cascades1,2. In the yeast Saccharomyces cerevisiae, Ste20 is involved in transmitting the mating-pheromone signal from the βγ-subunits (encoded by the STE4 and STE18 genes, respectively) of a heterotrimeric G protein to a downstream MAP kinase cascade1. We have identified a binding site for the G-protein β-subunit (Gβ) in the non-catalytic carboxy-terminal regions of Ste20 and its mammalian homologues, the p21-activated protein kinases (PAKs). Association of Gβ with this site in Ste20 was regulated by binding of pheromone to the receptor. Mutations in Gβ 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 Gβγ-mediated signal transduction in organisms ranging from yeast to mammals.

Suggested Citation

  • Thomas Leeuw & Cunle Wu & Joseph D. Schrag & Malcolm Whiteway & David Y. Thomas & Ekkehard Leberer, 1998. "Interaction of a G-protein β-subunit with a conserved sequence in Ste20/PAK family protein kinases," Nature, Nature, vol. 391(6663), pages 191-195, January.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6663:d:10.1038_34448
    DOI: 10.1038/34448
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