Role of yeast insulin-degrading enzyme homologs in propheromone processing and bud site selection.

The Saccharomyces cerevisiae AXL1 gene product Axl1p shares homology with the insulin-degrading enzyme family of endoproteases. Yeast axl1 mutants showed a defect in a-factor pheromone secretion, and a probable site of processing by Axl1p was identified within the a-factor precursor. In addition, Axl1p appears to function as a morphogenetic determinant for axial bud site selection. Amino acid substitutions within the presumptive active site of Axl1p caused defects in propheromone processing but failed to perturb bud site selection. Thus, Axl1p has been shown to participate in the dual regulation of distinct signaling pathways, and a member of the insulinase family has been implicated in propeptide processing.