Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy.
EMBO J
; 20(11): 2757-67, 2001 Jun 01.
Article
de En
| MEDLINE
| ID: mdl-11387209
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Sarcomères
/
Cardiomyopathie dilatée
/
Interleukine-6
/
Mitogen-Activated Protein Kinase Kinases
/
Mitogen-Activated Protein Kinases
/
Coeur
/
Myocarde
Limites:
Animals
/
Humans
Langue:
En
Journal:
EMBO J
Année:
2001
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique