P. Li et M. Mcleod, MOLECULAR MIMICRY IN DEVELOPMENT - IDENTIFICATION OF STE11(+) AS A SUBSTRATE AND MEI3(+) AS A PSEUDOSUBSTRATE INHIBITOR OF RAN1(+) KINASE, Cell, 87(5), 1996, pp. 869-880
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(+). Sequenc
e 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. T
hese results identify sequences critical for phosphorylation of ste11(
+) by ran1(+) and suggest that mei3(+) employs a pseudosubstrate mecha
nism for its inhibitory function.