| First Author | Nicol RL | Year | 2001 |
| Journal | EMBO J | Volume | 20 |
| Issue | 11 | Pages | 2757-67 |
| PubMed ID | 11387209 | Mgi Jnum | J:69910 |
| Mgi Id | MGI:2135732 | Doi | 10.1093/emboj/20.11.2757 |
| Citation | Nicol RL, et al. (2001) Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. EMBO J 20(11):2757-67 |
| abstractText | Mitogen-activated protein kinase (MAPK) pathways couple intrinsic and extrinsic signals to hypertrophic growth of cardiomyocytes. The MAPK kinase MEK5 activates the MAPK ERK5. To investigate the potential involvement of MEK5-ERK5 in cardiac hypertrophy, we expressed constitutively active and dominant-negative forms of MEK5 in cardiomyocytes in vitro. MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner. The cytokine leukemia inhibitory factor (LIF), which stimulates MEK5 activity, evoked a similar response. Moreover, a dominant-negative MEK5 mutant specifically blocked LIF-induced elongation of cardiomyocytes and reduced expression of fetal cardiac genes without blocking other aspects of LIF-induced hypertrophy. Consistent with the ability of MEK5 to induce serial assembly of sarcomeres in vitro, cardiac-specific expression of activated MEK5 in transgenic mice resulted in eccentric cardiac hypertrophy that progressed to dilated cardiomyopathy and sudden death. These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly. |
