Several proto-oncogenes have been designated as intermediates in signal transducing pathways and 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, we have identified a new class of potential oncogenes. The translational initiation factor 4E (eIF-4E) has been shown to induce tumors in nude mice and induce DNA synthesis and morphological transformation after microinjection into NIH 3T3 cells. The mitogenic activity of elF-4E as measured by DNA synthesis was enhanced 5-fold by co-injection with PKC and inhibited by co-injection with neutralizing anti-ras monoclonal antibodies. These results demonstrate a direct biological link between PKC and eIF-4E activity and also demonstrate a requirement for G-protein signal transduction in the activation of eIF-4E bioactivity.
