Molecular Mimicry in Development: Identification of ste11+ As a Substrate and mei3+ As a Pseudosubstrate Inhibitor of ran1+ Kinase

Abstract ran1 + (pat1 + ) kinase inhibits exit from the mitotic cell cycle and entry into meiosis. Inactivation of ran1 + by mei3 + is sufficient to precipitate the entire meiotic developmental program. Here, we show that the ste11 + transcription factor is a substrate for ran1 + in vitro and that this reaction is directly inhibited by mei3 + . Sequence comparison reveals that ste11 + contains two domains homologous to each other and to a domain of mei3 + . Mutagenesis studies reveal that the regions of homology contain substrate specificity determinants. These results identify sequences critical for phosphorylation of ste11 + by ran1 + and suggest that mei3 + employs a pseudosubstrate mechanism for its inhibitory function.