P70(S6K) P85(S6K) - MECHANISM OF ACTIVATION AND ROLE IN MITOGENESIS/

The p70(s6k)/p85(s6k) represent two isoforms of the same kinase which are derived by differential splicing from a common gene. The p85(s6k), isoform is identical to p70(s6k) except for a 23 amino acid extension at its N-terminus, which constitutively targets it do the nucleus. Bo th isoforms are activated by multisite phosphorylation in response to mitogens and reside on the same signaling pathway, a pathway which is distinct from that of p42(mapk)/p44(mapk) pathway. Inhibitory p70(s6k) /p85(s6k) antibodies or the immunosuppressant rapamycin selectively in hibit kinase activity and repress or abolish cell growth depending an the inhibitory agent employed and the cell type examined. Recent studi es imply that these effects are exerted through inhibition of 40S ribo somal protein S6 phosphorylation, the kinase target, which in turn sup presses the translation of a family of transcripts essential for cell growth.