Myosin light chain kinase mediates sarcomere organization during cardiac hypertrophy in vitro

During the development of hypertrophy, cardiac myocytes increase organizati on of the sarcomere, a highly ordered contractile unit in striated muscle c ells. Several hypertrophic agonists, such as angiotensin II, phenylephrine, and endothelin-1, have been shown to promote the sarcomere organization. H owever, the signaling pathway, which links extracellular stimuli to sarcome re organization, has not been clearly demonstrated. Here, we demonstrate th at myosin light chain kinase specifically mediates agonist-induced sarcomer e organization during early hypertrophic response. Acute administration of a hypertrophic agonist phenylephrine, or angiotensin II, causes phosphoryla tion of myosin light chain 2v both in cultured cardiac myocytes and in the adult heart in vivo. We also show that both sarcomere organization and myos in light chain 2v phosphorylation are dependent on the activation of Ca2+/c almodulin pathway, a known activator of myosin light chain kinase. These re sults define a new and specific role of myosin light chain kinase in cardia c myocytes, which may provide a rapid adaptive mechanism in response to hyp ertrophic stimuli.