Copyright X 1993, American Society for Microbiology Inhibition of Protein Kinase C 4 Subspecies Blocks the Activation of an NF-KB-Like Activity in

Nuclear factor KB (NF-KB) plays a critical role in the regulation of a large variety of cellular genes. However, the mechanism whereby this nuclear factor is activated remains to be determined. In this report, we present evidence that in oocytes from Xenopus laevis, (i) ras p21- and phospholipase C (PLC)-mediated phosphatidyl-choline (PC) hydrolysis activates NF-KB and (ii) protein kinase C C subspecies is involved in the activation of NF-cB in response to insulin/ras p21/PC-PLC. Thus, the microinjection of either ras p21 or PC-PLC, or the exposure of oocytes to insulin, promotes a significant translocation to the nucleus of an NF-KB-like activity. This effect is not observed when oocytes are incubated with phorbol myristate acetate or progesterone, both of which utilize a ras p21-independent pathway for oocyte activation. These data strongly suggest a critical role of the insulin/ras p21/PC-PLC/protein kinase C C pathway in the control of NF-KB activation. Although nuclear factor KB (NF-KB) was originally iden-tified as a complex binding to the KB enhancer element of the gene coding for the immunoglobulin light chain (35), it now seems apparent that it is involved in the regulation of a relatively large variety of cellular genes (for reviews, see references 16 and 22). An important example is the bindin