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

[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.

[学科分类] 生物化学/生物物理

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