Essential role of PDK1 in regulating cell size and development in mice

Margaret A. Lawlor (Lead / Corresponding author), Alfonso Mora, Peter R. Ashby, Michayla R. Williams, Victoria Murray-Tait, Lorraine Malone, Alan R. Prescott, John M. Lucocq, Dario R. Alessi

    Research output: Contribution to journalArticle

    251 Citations (Scopus)

    Abstract

    PDK1 functions as a master kinase, phosphorylating and activating PKB/Akt, S6K and RSK. To learn more about the roles of PDK1, we generated mice that either lack PDK1 or possess PDK1 hypomorphic alleles, expressing only ∼10% of the normal level of PDK1. PDK1-/- embryos die at embryonic day 9.5, displaying multiple abnormalities including lack of somites, forebrain and neural crest derived tissues; however, development of hind- and midbrain proceed relatively normally. In contrast, hypomorphic PDK1 mice are viable and fertile, and insulin injection induces the normal activation of PKB, S6K and RSK. Nevertheless, these mice are 40-50% smaller than control animals. The organ volumes from the PDK1 hypomorphic mice are reduced proportionately. We also establish that the volume of a number of PDK1-deficient cells is reduced by 35-60%, and show that PDK1 deficiency does not affect cell number, nuclear size or proliferation. We provide genetic evidence that PDK1 is essential for mouse embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin's ability to activate PKB, S6K and RSK.

    Original languageEnglish
    Pages (from-to)3728-3738
    Number of pages11
    JournalEMBO Journal
    Volume21
    Issue number14
    DOIs
    Publication statusPublished - 15 Jul 2002

    Keywords

    • Cell growth
    • Cell size
    • Embryonic development
    • PDK1
    • PI 3-kinase
    • PKB-Akt

    Fingerprint Dive into the research topics of 'Essential role of PDK1 in regulating cell size and development in mice'. Together they form a unique fingerprint.

  • Cite this

    Lawlor, M. A., Mora, A., Ashby, P. R., Williams, M. R., Murray-Tait, V., Malone, L., Prescott, A. R., Lucocq, J. M., & Alessi, D. R. (2002). Essential role of PDK1 in regulating cell size and development in mice. EMBO Journal, 21(14), 3728-3738. https://doi.org/10.1093/emboj/cdf387