MO25α/β interact with STRADα/β enhancing their ability to bind, activate and localize LKB1 in the cytoplasm

Jérôme Boudeau (Lead / Corresponding author), Annette F. Baas, Maria Deak, Nick A. Morrice, Agnieszka Kieloch, Mike Schutkowski, Alan R. Prescott, Hans C. Clevers, Dario R. Alessi

    Research output: Contribution to journalArticlepeer-review

    371 Citations (Scopus)


    Mutations in the LKB1 protein kinase result in the inherited Peutz Jeghers cancer syndrome. LKB1 has been implicated in regulating cell proliferation and polarity although little is known about how this enzyme is regulated. We recently showed that LKB1 is activated through its interaction with STRADα, a catalytically deficient pseudokinase. Here we show that endogenous LKB1-STRADα complex is associated with a protein of unknown function, termed MO25α, through the interaction of MO25α with the last three residues of STRADα. MO25α and STRADα anchor LKB1 in the cytoplasm, excluding it from the nucleus. Moreover, MO25α enhances the formation of the LKB1-STRADα complex in vivo, stimulating the catalytic activity of LKB1∼10-fold. We demonstrate that the related STRADβ and MO25β isoforms are also able to stabilize LKB1 in an active complex and that it is possible to isolate complexes of LKB1 bound to STRAD and MO25 isoforms, in which the subunits are present in equimolar amounts. Our results indicate that MO25 may function as a scaffolding component of the LKB1-STRAD complex and plays a crucial role in regulating LKB1 activity and cellular localization.

    Original languageEnglish
    Pages (from-to)5102-5114
    Number of pages13
    JournalEMBO Journal
    Issue number19
    Publication statusPublished - 1 Oct 2003


    • Cell growth
    • Mass spectrometry
    • Peutz Jeghers syndrome
    • Protein interactions
    • Signal transduction

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • General Immunology and Microbiology
    • General Biochemistry,Genetics and Molecular Biology


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