Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in Saccharomyces cerevisiae that controls spore morphogenesis. Similar to other MAPKs, it is controlled by dual phosphorylation of its T-X-Y activation motif. However, Smk1 is not phosphorylated by a prototypical MAPK kinase. Here, we show that the T residue in Smk1's activation motif is phosphorylated by the cyclin-dependent kinase (CDK)-activating kinase, Cak1. The Y residue is autophosphorylated in an independent intramolecular reaction that requires the meiosis-specific protein Ssp2. Although both SMK1 and SSP2 are expressed as middle-meiosisspecific genes, Smk1 protein starts to accumulate before Ssp2. Thus, Smk1 exists in a low-activity (pT) form early in sporulation and a high-activity (pT/pY) form later in the program. Ssp2 must be present when Smk1 is being produced to activate the autophosphorylation reaction, suggesting that Ssp2 acts through a transitional intermediate form of Smk1. These findings provide a mechanistic explanation for how Smk1 activity thresholds are generated. They demonstrate that intramolecular autophosphorylation of MAPKs can be regulated and suggest new mechanisms for coupling MAPK outputs to developmental programs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.