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PLoS One

Title:		The ankyrin repeats and DHHC S-acyl transferase domain of AKR1 act independently to regulate switching from vegetative to mating states in yeast
Author(s):		Hemsley PA; Grierson CS;
Address:		"School of Biological Sciences, University of Bristol, Bristol, United Kingdom. piers.hemsley@bristol.ac.uk"
Journal Title:		PLoS One
Year:		2011
Volume:		20111208
Issue:		12
Page Number:		e28799 -
DOI:		10.1371/journal.pone.0028799
ISSN/ISBN:		1932-6203 (Electronic) 1932-6203 (Linking)
Abstract:		"Signal transduction from G-protein coupled receptors to MAPK cascades through heterotrimeric G-proteins has been described for many eukaryotic systems. One of the best-characterised examples is the yeast pheromone response pathway, which is negatively regulated by AKR1. AKR1-like proteins are present in all eukaryotes and contain a DHHC domain and six ankyrin repeats. Whilst the DHHC domain dependant S-acyl transferase (palmitoyl transferase) function of AKR1 is well documented it is not known whether the ankyrin repeats are also required for this activity. Here we show that the ankyrin repeats of AKR1 are required for full suppression of the yeast pheromone response pathway, by sequestration of the Gbetagamma dimer, and act independently of AKR1 S-acylation function. Importantly, the functions provided by the AKR1 ankyrin repeats and DHHC domain are not required on the same molecule to fully restore WT phenotypes and function. We also show that AKR1 molecules are S-acylated at locations other than the DHHC cysteine, increasing the abundance of AKR1 in the cell. Our results have important consequences for studies of AKR1 function, including recent attempts to characterise S-acylation enzymology and kinetics. Proteins similar to AKR1 are found in all eukaryotes and our results have broad implications for future work on these proteins and the control of switching between Gbetagamma regulated pathways"
Keywords:		"Acylation Acyltransferases/*chemistry/*metabolism *Ankyrin Repeat Cysteine/metabolism Enzyme Stability GTP-Binding Protein beta Subunits/metabolism Genes, Mating Type, Fungal/*genetics Genes, Switch/*genetics Genetic Complementation Test Models, Biologica;"
Notes:		"MedlineHemsley, Piers A Grierson, Claire S eng BB/D013585/1/Biotechnology and Biological Sciences Research Council/United Kingdom Research Support, Non-U.S. Gov't 2011/12/17 PLoS One. 2011; 6(12):e28799. doi: 10.1371/journal.pone.0028799. Epub 2011 Dec 8"