Identification of a second-site suppressor mutation of the GTPase defect associated with McCune - Albright syndrome: A model using the yeast heterotrimeric G protein, GPA1

Laura S. Ooms, Matthew J. Koster, Joshua R. Mitchell, Robin Pals-Rylaarsdam

Research output: Contribution to journalArticle

2 Scopus citations


McCune - Albright syndrome (MAS) causes a variety of bone and endocrine abnormalities due to the post-zygotic mutation of the alpha subunit of the stimulatory G-protein Gsα. This mutation causes signal-independent activity of the G-protein in the affected cells. We report the development of a system to study the effects of MAS mutations using Saccharomyces cerevisiae, wherein activation of the yeast G-protein pathway results in growth arrest in a genetically recessive fashion. We introduced the MAS mutation into the analogous site in the yeast Gα gene, GPA1 and randomly mutated the gene to produce intragenic suppressors. Yeast with normal and mutated G-protein genes were induced to lose the normal gene, and mutations able to intragenically suppress the constitutive activity of the MAS mutation were identified based on their ability to form colonies. We report one mutation in GPA1, also in the active site, that is an intragenic suppressor of the MAS defect.

Original languageEnglish (US)
Pages (from-to)166-173
Number of pages8
JournalArchives of Physiology and Biochemistry
Issue number3
StatePublished - Jun 1 2006



  • G-protein
  • GPA1
  • McCune - Albright syndrome
  • Mutation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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