Exp Mol Med.  2006 Apr;38(2):180-189.

Implication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytes

• Choi YO
• Ryu HJ
• Kim HR
• Song YS
• Kim C
• Lee W
• Choe H
• Leem CH
• Jang YJ

Abstract

In adipocytes, insulin stimulates glucose transport primarily by promoting the translocation of GLUT4 to the plasma membrane. Requirements for Ca2+/ calmodulin during insulin-stimulated GLUT4 translocation have been demonstrated; however, the mechanism of action of Ca2+ 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 Ca2+/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 Ca2+-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 Ca2+/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes.

Keyword

calcium signaling; glucose transporter type 4; insulin; myosin type II; myosin-light-chain kinase; phosphorylation

MeSH Terms

Protein Transport/drug effects
Phosphorylation
Naphthalenes/pharmacology
Myosin-Light-Chain Kinase/antagonists & inhibitors/*metabolism
Myosin Type II/*metabolism
Mice
Insulin/*pharmacology
Glucose Transporter Type 4/*metabolism
Enzyme Inhibitors/pharmacology
Dose-Response Relationship, Drug
Calmodulin/antagonists & inhibitors/physiology
Azepines/pharmacology
Animals
Adipocytes/cytology/*drug effects/metabolism
3T3 Cells