Differential stimulation of PKC phosphorylation 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 Kv beta 2 subunits of potassium channel and protein kinase C (PKC) zeta, thereby acting as a physical link in the assembly of PKC zeta-ZIP-potassium channel complexes. ZIP1 and ZIP2 differentially stimulate phosphorylation of Kv beta 2 by PKC zeta. They also interact to form heteromultimers, which allows for a hybrid stimulatory activity to PKC zeta. 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 PKC zeta-targeted phosphorylation.