The products of oncogenes have been categorized by structural/functional criteria and biological activity into four groups: 1) growth factors and their receptors; 2) signal transducing G proteins; 3) cytoplasmic serine/threonine protein kinases; and 4) nuclear factors involved in transcriptional regulation. Recently, oncogene products have been described that do not fit into these categories, e.g., translational initiation factor-4E (eIF-4E). eIF-4E has been shown to induce tumors in nude mice and induce DNA synthesis and morphological transform after microinjection into NIH 3T3 cells. The DNA synthesis inducing activity of eIF-4E was shown to be enhanced 5-fold by co-injection with protein kinase C (PKC) and inhibited by co-injection with neutralizing anti-ras monoclonal antibody or the dominant negative ras mutant (Asn17). These results demonstrate a direct biological link between PKC and eIF-4E activity and also demonstrate a requirement for ras in the activation of eIF-4E bioactivity.
