Ro 31‐6045, the inactive analogue of the protein kinase C inhibitor Ro 31‐8220, blocks in vivo activation of p70s6k/p85s6k: implications for the analysis of S6K signalling

FEBS Letters

Pearson, Richard B¹  Marmy-Conus, Nelly¹  Hannan, Katherine M¹ 

[1] Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Locked Bag #1, A'Beckett Street, Melbourne, Vic. 8006, Australia

关键词: Protein kinase inhibitor;    p70s6k/p85s6k;    Bisindolylmaleimide;    Ro 31-6045;    mTOR;   

DOI  :  10.1016/S0014-5793(02)02738-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The mitogen-stimulated protein kinase p70^s6k/p85^s6k (S6K) plays an essential role in cell proliferation and growth, with inhibitors of the S6K signalling pathway showing promise as anti-tumour therapeutics. Here, we report that the bisindolylmaleimide derivative Ro 31-6045, previously reported to be inactive as a kinase inhibitor, inhibited S6K activity in vivo with an IC₅₀=8 μM. Structure/function analysis using mutant forms of S6K indicates that Ro 31-6045 inhibition is independent of the upstream activator mTOR. Ro 31-6045 will prove useful in elucidating the complex activation mechanism of S6K and its independence from mTOR will allow confirmation of functional data obtained using the mTOR inhibitor rapamycin.

【 授权许可】

Unknown