p70s6k/p85s6k: mechanism of activation and role in mitogenesis

Abstract

The p70s6k/p85s6k represent two isoforms of the same kinase which are derived by differential splicing from a common gene. The p85s6k isoform is identical to p70s6k except for a 23 amino acid extension at its N-terminus, which constitutively targets it to the nucleus. Both 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 p42mapk/p44mapk pathway. Inhibitory p70s6k/p85s6k antibodies or the immunosuppressant rapamycin selectively inhibit kinase activity and repress or abolish cell growth depending on the inhibitory agent employed and the cell type examined. Recent studies imply that these effects are exerted through inhibition of 40S ribosomal protein S6 phosphorylation, the kinase target, which in turn suppresses the translation of a family of transcripts essential for cell growth.