Open AccessImplication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytes
Author(s) -
Young-Hyun Choi,
Hee Jeong Ryu,
Hye Rim Kim,
Yong Jin Song,
Cheonghwan Kim,
Wan Lee,
Han Choe,
Chae Hun Leem,
Yeon Jin Jang
Publication year - 2006
Publication title -
experimental and molecular medicine/experimental and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.703
H-Index - 82
eISSN - 2092-6413
pISSN - 1226-3613
DOI - 10.1038/emm.2006.22
Subject(s) - glut4 , myosin light chain kinase , calmodulin , insulin , myosin , chromosomal translocation , glucose uptake , phosphorylation , glucose transporter , microbiology and biotechnology , insulin receptor , medicine , biology , chemistry , endocrinology , biochemistry , insulin resistance , enzyme , gene
In adipocytes, insulin stimulates glucose transport primarily by promoting the translocation of GLUT4 to the plasma membrane. Requirements for Ca(2+)/calmodulin during insulin-stimulated GLUT4 translocation have been demonstrated; however, the mechanism of action of Ca(2+) in this process is unknown. Recently, myosin II, whose function in non-muscle cells is primarily regulated by phosphorylation of its regulatory light chain by the Ca(2+)/calmodulin-dependent myosin light chain kinase (MLCK), was implicated in insulin-stimulated GLUT4 translocation. The present studies in 3T3-F442A adipocytes demonstrate the novel finding that insulin significantly increases phosphorylation of the myosin II RLC in a Ca(2+)-dependent manner. In addition, ML-7, a selective inhibitor of MLCK, as well as inhibitors of myosin II, such as blebbistatin and 2,3-butanedione monoxime, block insulin-stimulated GLUT4 translocation and subsequent glucose transport. Our studies suggest that MLCK may be a regulatory target of Ca(2+)/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes.