PROTEIN KINASE-C-ZETA AND KINASE-C-ETA IN MURINE EPIDERMIS - TPA INDUCES DOWN-REGULATION OF PKC-ETA BUT NOT PKC-ZETA

Murine epidermis contains PKC-zeta and eta as evidenced by the application of specific antisera. PKC-zeta predominates in the cytosol and PKC-eta in the particulate fraction. PKC-zeta is shown to be present also in other murine tissues, with large amounts found in lung. Whereas epidermal PKC-eta is completely down-regulated by treatment of mouse skin with TPA or bryostatin 1 for 18 h, PKC-zeta is neither translocated by treatment with TPA for 20 min, nor down-regulated by treatment with TPA or bryostatin 1 for 18 h. PKC-zeta is activated by phosphatidyl serine alone and does neither respond to Ca2+ nor to TPA. It is inhibited by staurosporine with an IC50 of 16 nM, which is within the same range of other PKC isoenzymes. The sensitivity of PKC-zeta towards the staurosporine derivative K252a is similar to that of PKC-alpha,beta,gamma but much higher than that of PKC-delta and epsilon.