Molecular mimicry in development: Identification of ste11(+) as a substrate and mei3(+) as a pseudosubstrate inhibitor of ran1(+) kinase

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.