Phosphoregulation of the novel hemi-arrestin MAPK scaffold Sms1 prevents untimely mating.

Mitogen-activated protein kinases (MAPK) are ancestral kinases that form essential signalling cascades. However, scaffolds that recruit kinases to subcellular locations and promote signal transduction have only been described in a few species. Notably, no scaffold was thought necessary for the MAPK cascade promoting sexual differentiation in fission yeast. Here, we identify the hemi-arrestin protein Sms1 as a novel scaffold of this MAPK cascade. Interactions with PIP2 and the pheromone receptor-coupled Gα subunit target Sms1 to plasma membrane patches, where it assembles the active cascade by binding each MAP kinase. These interactions are essential for signal transduction and local signal interpretation for polarised growth. Phosphorylation, including by the MAPK itself, antagonises Sms1 membrane translocation, establishing a negative feedback that underlies polarity patch turnover and prevents untimely mating attempts. Thus, Sms1 is a MAPK scaffold with canonical functions despite its distinct structural fold, highlighting convergent evolution of MAPK scaffolds across eukaryotes.