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Mechano-transduction to muscle protein synthesis is modulated by FAK

Klossner, Stephan ; Durieux, Anne-Cecile ; Freyssenet, Damien ; Flueck, Martin

In: European Journal of Applied Physiology, 2009, vol. 106, no. 3, p. 389-398

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    Title
    • Mechano-transduction to muscle protein synthesis is modulated by FAK
    Author
    • Klossner, Stephan. Institute of Anatomy, University of Berne, Berne, Switzerland
    • Durieux, Anne-Cecile. Institute of Anatomy, University of Berne, Berne, Switzerland
    • Freyssenet, Damien. Faculté de Médecine, Université Jean Monnet, Saint-Etienne, France
    • Flueck, Martin. Institute of Anatomy, University of Berne, Berne, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • European Journal of Applied Physiology, 2009, vol. 106, no. 3, p. 389-398. Springer-Verlag
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:320434
    Summary
    We examined the involvement of focal adhesion kinase (FAK) in mechano-regulated signalling to protein synthesis by combining muscle-targeted transgenesis with a physiological model for un- and reloading of hindlimbs. Transfections of mouse tibialis anterior muscle with a FAK expression construct increased FAK protein 1.6-fold versus empty transfection in the contralateral leg and elevated FAK concentration at the sarcolemma. Altered activation status of phosphotransfer enzymes and downstream translation factors showed that FAK overexpression was functionally important. FAK auto-phosphorylation on Y397 was enhanced between 1 and 6h of reloading and preceded the activation of p70S6K after 24h of reloading. Akt and translation initiation factors 4E-BP1 and 2A, which reside up- or downstream of p70S6K, respectively, showed no FAK-modulated regulation. The findings identify FAK as an upstream element of the mechano-sensory pathway of p70S6K activation whose Akt-independent regulation intervenes in control of muscle mass by mechanical stimuli in humans