A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCζ signaling and cell transformation
The structure of protein kinase C zeta (PKC zeta) is unusual with respect to other PKCs, as it lacks the C2 domain and possesses only one zinc finger region. Consequently, PKC zeta can not be activated by diacylglycerol or phorbol esters and is not downregulated by prolonged treatment by phorbol esters nor blocked by commonly utilized PKC inhibitors. In this study, we have explored the idea that PKC zeta might participate in proliferative pathways. Our findings show that marked overexpression of mammalian PKC zeta does not alter the growth characteristics of NIH 3T3 cells, nor induces cellular transformation. Furthermore, mammalian PKC zeta does not potentiate the transforming ability of oncogenes such as ras, sis and the muscarinic receptor m1. In this context, PKC zeta or its dominant negative mutant do not affect MAP kinase activation by oncogenes or growth factors. Taken together, our findings demonstrate that mammalian PKC zeta does not directly participate in signaling pathways involved in oncogenic transformation.