The reversible phosphorylation of proteins is a major regulatory mechanism that controls cell cycle progression and development in all eukaryotic organisms. Meiosis and spore formation in yeast (sporulation) provides an outstanding model system to study protein kinase signaling pathways. Similar to developmental programs in higher eukaryotes, induction of sporulation is controlled by a combination of cell-type and environmental signals. Once initiated, a transcriptional cascade of cell-type specific genes ultimately leads to a cell that is genetically and biochemically distinct from the starting cell. A protein kinase network has been identified that controls multiple steps in meiotic development. A central component of this network is the activating kinase Cak1. During sporulation Cak1 is required for activation of the MAP kinase homolog Smk1, the CDK-like kinase Ime2, and the CDK Cdc28. The CAK1, IME2 and SMK1 genes are tightly regulated by the transcriptional cascade of sporulation. This network controls meiotic progression at multiple self-reinforcing steps through DNA-binding and chromatin-modifying regulatory proteins. The goal of this proposal is to identify new components of the Cak1/Ime2/Smk1 protein kinase network, to elucidate molecular mechanisms that control its activities, and to identify targets that couple signaling to meiotic progression.
The specific aims of the proposal are: 1- Elucidate how Cak1 activates the Smk1 MAP kinase. 2- Elucidate how Ime2 is regulated by phosphorylation 3- Elucidate molecular mechanisms that regulate mid-late sporulation-specific gene expression, and 4- Identify negative regulators of the Smk1 pathway using genetic suppression approaches. These studies will provide mechanistic insights into how protein kinase networks control developmental programs in general and meiotic development in particular.
