FEBS Letters | |
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 | |
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 p70s6k/p85s6k (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
【 预 览 】
Files | Size | Format | View |
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RO201912020311820ZK.pdf | 290KB | download |