AKR1 encodes a candidate effector of the Gβγ complex in the Saccharomyces cerevisiae pheromone response pathway and contributes to control of both cell shape and signal transduction

Peter M. Pryciak, Leland H. Hartwell

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Mating pheromones of Saccharomyces cerevisiae control both signal transduction events and changes in cell shape. The Gβγ complex of the pheromone receptor-coupled G protein activates the signal transduction pathway, leading to transcriptional induction and cell cycle arrest, but how pheromone-dependent signalling leads to cell shape changes is unclear. We used a two-hybrid system to search for proteins that interact with the Gβγ complex and that might be involved in cell shape changes. We identified the ankyrin repeat-containing protein Akr1p and show here that it interacts with the free Gβγ complex. This interaction may be regulated by pheromone, since Akr1p is excluded from the Gαβγ heterotrimer. Both haploid and diploid cells lacking Akr1p grow slowly and develop deformed buds or projections, suggesting that this protein participates in the control of cell shape. In addition, Akr1p has a negative influence on the pheromone response pathway. Epistasis analysis demonstrates that this negative effect does not act on the Gβγ complex but instead affects the kinase cascade downstream of Gβγ, so that the kinase Ste20p and components downstream of Ste20p (e.g., Ste11p and Ste7p) are partially activated in cells lacking Akr1p. Although the elevated signalling is eliminated by deletion of Ste20p (or components downstream of Ste20p), the growth and morphological abnormalities of cells lacking Akr1p are not rescued by deletion of any of the known pheromone response pathway components. We therefore propose that Akr1p negatively affects the activity of a protein that both controls cell shape and contributes to the pheromone response pathway upstream of Ste20p but downstream of Gβγ. Specifically, because recent evidence suggests that Bem1p, Cdc24p, and Cdc42p can act in the pheromone response pathway, we suggest that Akr1p affects the functions of these proteins, by preventing them from activating mating-specific targets including the pheromone-responsive kinase cascade, until Gβγ is activated by pheromone.

Original languageEnglish (US)
Pages (from-to)2614-2626
Number of pages13
JournalMolecular and cellular biology
Volume16
Issue number6
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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