This latter finding is of particular importance as previous studies have demonstrated that LKB1 is nuclear localized and sequestered from its cytosolic targets such as AMPK. In contrast, coexpression of STRAD with LKB1 in culture cell systems results in nuclear export of the LKB1/STRAD/MO25 ternary complex, suggesting that the assembly state of the LKB1 subunit complex is responsible for nuclear export. However, whether this interaction has any physiological BAY 43-9006 meanings is still controversial since we were unable to show any significant difference in STRAD or MO25 expression or association with LKB1 in physiologic conditions. On the other hand, we have shown that inhibition of Fyn kinase efficiently upregulates AMPK activity through LKB1 redistribution. Thus, the regulation of Fyn binding/phosphorylation of LKB1 can account for the normal physiologic regulation of nuclear LKB1 export. The role of Fyn-LKB1 interaction in the control of AMPK and downstream signalling in cultured C2C12 myotubes and skeletal muscle in vivo was clearly demonstrated by using a cell permeable synthetic peptide of the LKB1 proline-rich domain. This peptide was able to dissociate Fyn from LKB1 and importantly, it increased the phosphorylation levels of the activating site of the AMPK a subunit resulting in increased AMPK activity, as detected by phosphorylation of the specific AMPK substrate ACC. This latter finding also suggests that developing novel therapeutic approaches that disrupt the Fyn-LKB1 interaction will have the biological effect of activating AMPK, a pathway that in principal will increase fatty acid utilization and improve insulin sensitivity in peripheral tissues. In summary, this study has identified the structural elements responsible for the direct binding interaction between the tyrosine kinase Fyn and the LKB1 catalytic subunit that is primarily responsible for the activation of the energy-sensing AMPK. Disruption of this interaction using LKB1-proline rich domain mimicking peptides recapitulates the pharmacological effects of Fyn kinase inhibition/deletion in vitro and in vivo. MicroRNAs are abundant small RNA molecules that act as post-transcriptional regulators of gene expression in higher organisms. Two properties of miRNAs make them especially promising as extracellular disease biomarkers. Firstly, miRNAs act as master regulators of cellular pathways. Therefore, by measuring miRNA expression, inferences can be made about pathophysiological processes in the tissue of origin. Secondly, miRNAs exhibit remarkable stability in extracellular biofluids such as serum on account of their association with proteins/lipoproteins or by encapsulation within extracellular vesicles. Serum miRNAs have attracted much interest as biomarkers for a wide range of disease conditions, especially in the case of human malignancy.