Differential Stimulation of PKC Phosphorylatio of Potassium Channels by ZIP1 and ZIP2

Targeting of protein modification enzymes is a key biochemical step to achieve specific and effective posttranslational modifications. Two alternatively spliced ZIP1 and ZIP2 proteins are described, which bind to both Kvβ2 subunits of potassium channel and protein kinase C (PKC) ζ, thereby acting as a physical link in the assembly of PKCζ-ZIP-potassium channel complexes. ZIP1 and ZIP2 differentially stimulate phosphorylation of Kvβ2 by PKCζ. They also interact to form heteromultimers, which allows for a hybrid stimulatory activity to PKCζ. Finally, ZIP1 and ZIP2 coexist in the same cell type and are elevated differentially by neurotrophic factors. These results provide a mechanism for specificity and regulation of PKCζ-targeted phosphorylation.