| First Author | Muchir A | Year | 2009 |
| Journal | Biochim Biophys Acta | Volume | 1792 |
| Issue | 1 | Pages | 75-81 |
| PubMed ID | 19022376 | Mgi Jnum | J:143904 |
| Mgi Id | MGI:3829321 | Doi | 10.1016/j.bbadis.2008.10.012 |
| Citation | Muchir A, et al. (2009) Reduced expression of A-type lamins and emerin activates extracellular signal-regulated kinase in cultured cells. Biochim Biophys Acta 1792(1):75-81 |
| abstractText | Background: Mutations in genes encoding A-type lamins and emerin cause cardiomyopathy and muscular dystrophy. We previously showed activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) cascade in hearts of mice with mutations in these genes. Here, we tested the hypothesis that reducing A-type lamins and emerin in cultured cells activate ERK signaling. Methods: We used siRNA to knockdown A-type lamins and emerin in HeLa and C2C12 cells. Activation of ERK was assessed by immunoblotting and immunofluorescence microscopy with antibodies against phosphorylated protein and by using real-time RT-PCR to measure RNAs encoded by genes for transcription factors stimulated by ERK. Results: Knockdown of A-type lamins and emerin in HeLa and C2C12 stimulated phosphorylation and nuclear translocation of ERK as well as activation of genes encoding downstream transcription factors. A MAPK/ERK kinase (MEK) inhibitor reduced ERK phosphorylation in cells with reduced expression of A-type lamins and emerin. Conclusions: These results provide proof for the hypothesis that altered expression of emerin and A-type lamins activates ERK signaling, which in turn can cause cardiomyopathy. General significance: ERK is a potential target for the pharmacological treatment of cardiomyopathy caused by mutations in the genes encoding emerin and A-type lamins. |
