title: Activation of the Smk1 mitogen-activated protein kinase by developmentally regulated autophosphorylation.
abstract: 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-meiosis-specific 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Whinston
authors.forename: Gregory
authors.initials: G
authors.lastname: Omerza
authors.forename: Amrita
authors.initials: A
authors.lastname: Singh
authors.forename: Chong Wai
authors.initials: CW
authors.lastname: Tio
authors.forename: Edward
authors.initials: E
authors.lastname: Winter
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: C460039:SSP2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases; C443670:Smk1 protein, S cerevisiae; D000095043:Cyclin-Dependent Kinase-Activating Kinase