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

Nelly Marmy-Conus, Katherine M. Hannan, Richard B. Pearson

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)135-140
Number of pages6
JournalFEBS Letters
Volume519
Issue number1-3
DOIs
Publication statusPublished - 22 May 2002
Externally publishedYes

Keywords

  • Bisindolylmaleimide
  • mTOR
  • p70/p85
  • Protein kinase inhibitor
  • Ro 31-6045

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