Figure 6.—

A model for signaling interactions that connect the Ras/cAMP pathway, Ime2, Smk1, and the transcriptional program of sporulation. The early (Ime1-inducible), and middle (Ndt80-inducible) phases of the transcriptional program of meiosis are indicated by horizontal lines. High levels of glucose lead to high PKA activity that inhibits IME1 and prevents meiotic initiation (top). The regulation of the Smk1 pathway by PKA occurs only in the presence of intermediate levels of glucose that are insufficient to prevent meiotic initiation (middle). In the intermediate state PKA is shown to negatively regulate Smk1 directly, through Ime2, or through both mechanisms as discussed in the text (dotted lines). Ime2 is shown to activate the Smk1 pathway through Ndt80-dependent and Ndt80-independent mechanisms. The Ndt80-independent mechanism is largely based on the relatively rapid kinetics of Smk1 inhibition by Bn-PP1 in the ime2-as1 strain and therefore should be considered provisional (dotted lines). Transition to a low PKA state (bottom) is predicted to relieve inhibition and increase Smk1 activity through the pathways indicated.