Mechano-transduction to muscle protein synthesis is modulated by FAK
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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 6 h of reloading and preceded the activation of p70S6K after 24 h 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.
KeywordsFocal adhesion kinase S6 kinase Akt eIF4E-BP1 Gene electrotransfer
Special thanks are addressed to the personal of the University of Berne: PhD Sonja Mund and David Haberthür for their work in breeding and housing the animals. We also acknowledge the assistance of PhD Michael Altmann from the Institute for Biochemistry and Molecular Biology and PhD Jürg Reichen from the Department of Clinical Pharmacology and PhD Oliver Baum from the Institute of Anatomy for their technical advices. This study was supported by the Swiss National Science Foundation and a start up grant from the Manchester Metropolitan University.
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