Regulation and localization of ribosomal protein S6 kinase 1 isoforms

Abstract

Ribosomal protein S6 kinase 1 (S6K1), a critical mediator of cell growth, is overexpressed in breast cancer and is associated with poor prognosis. S6K1 has two known isoforms, p85^S6K1 and p70^S6K1. p85^S6K1 is characterized by 23 additional amino acids in the N-terminus of p70^S6K1. This is thought to target p85^S6K1 to the nucleus, while p70^S6K1 is mainly cytoplasmic. We sought to determine the activation, regulation, and function of p70^S6K1 and p85^S6K1 in breast cancer. We found that most breast cancer cell lines expressed both isoforms. Mitogen-dependent pathways concordantly regulated phosphorylation on T389, S371, and T421/S424. Phosphorylation of both isoforms was inhibited by PI3K/mTOR inhibitors. Mitogen-dependent pathways concordantly regulated the phosphorylation of the two isoforms on T389, S371, and T421/S424. Both isoforms had S6 kinase activity. We also detected a p60 isoform with antibodies to the p70^S6K1 C-terminal but not the N-terminal. Further studies on S6K1 isoforms are warranted for therapeutically targeting this pathway.

• mTOR
• p85S6K1
• p70S6K1
• ribosomal S6 kinase
• cell growth

Notes

^†Dr Kim is currently affiliated with the Breast Center, Kangseo Miz Medi Hospital, Miz Medi Hospital, 701-4 Naebalsan-dong, Kangseo-ku, 157-723, Seoul, South Korea.