2. Author's Information
    Laura R. Pearce
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.

    Gordon R. Alton
    Pfizer Global Research and Development, San Diego, CA 92121, U.S.A.

    Daniel T. Richter
    Pfizer Global Research and Development, San Diego, CA 92121, U.S.A.

    John C. Kath
    Pfizer Global Research and Development, San Diego, CA 92121, U.S.A.

    Laura Lingardo
    Pfizer Global Research and Development, San Diego, CA 92121, U.S.A.

    Justin Chapman
    Pfizer Global Research and Development, San Diego, CA 92121, U.S.A.

    Catherine Hwang
    Pfizer Global Research and Development, San Diego, CA 92121, U.S.A.

    Dario R. Alessi
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
  3. Abstract
    S6K1 (p70 ribosomal S6 kinase 1) is activated by insulin and growth factors via the PI3K (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin) signalling pathways. S6K1 regulates numerous processes, such as protein synthesis, growth, proliferation and longevity, and its inhibition has been proposed as a strategy for the treatment of cancer and insulin resistance. In the present paper we describe a novel cell-permeable inhibitor of S6K1, PF-4708671, which specifically inhibits the S6K1 isoform with a Ki of 20 nM and IC50 of 160 nM. PF-4708671 prevents the S6K1-mediated phosphorylation of S6 protein in response to IGF-1 (insulin-like growth factor 1), while having no effect upon the PMA-induced phosphorylation of substrates of the highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases. PF-4708671 was also found to induce phosphorylation of the T-loop and hydrophobic motif of S6K1, an effect that is dependent upon mTORC1 (mTOR complex 1). PF-4708671 is the first S6K1-specific inhibitor to be reported and will be a useful tool for delineating S6K1-specific roles downstream of mTOR.
    Keywords
    Akt/protein kinase B (PKB), cancer, kinase inhibitor, phosphoinositide 3-kinase (PI3K), p70 ribosomal S6 kinase (S6K), serum- and glucocorticoid-induced protein kinase (SGK)
    DOI: 10.1042/BJ20101024
    ADLID: 27601-v4
  4. Post New Comments

  1. Back to Results
  1. Keywords
    Akt/protein kinase B (PKB) cancer kinase inhibitor phosphoinositide 3-kinase (PI3K) p70 ribosomal S6 kinase (S6K) serum- and glucocorticoid-induced protein kinase (SGK)
Want to Index your journal in the ADL?

The Asian Digital Library (ADL) has now aligned its quality criterion of indexing with JournalsPedia. The ADL will index only those journals verified and enlisted by the Jorunalspedia. So please submit your journal first to JournalsPedia to get recognition and content quality confirmation.


Suggest a Journal

© Copyright 2020 The ADL