Identification and functional characterization of polo-like kinase 2 autoregulatory sites

Polo family kinases play important roles in cellular proliferation as well as neuronal synaptic plasticity. However, the posttranslational regulation of these kinases is not fully understood. Here, we identified several novel Plk2 phosphorylation sites stimulated by Plk2 itself. By site-directed mutagenesis, we uncovered three additional hyperactivating Plk2 mutations as well as a series of residues regulating Plk2 steady-state expression level. Because of the established role of Plk2 in homeostatic negative control of excitatory synaptic strength, these phosphorylation sites could play an important role in the rapid activation, expansion, and prolongation of Plk2 signaling in this process.

▶Active, but not kinase-dead, forms of Plk2 are highly phosphorylated. ▶Mutating Plk2 phosphorylation sites demonstrates regulation of protein stability. ▶Plk2 phosphorylation sites regulate kinase activity toward Plk2 substrate SPAR. ▶Plk2 phosphosite mutants regulate dendritic spine stability in hippocampal neurons.