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Olga Kotova

Olga Kotova

Research engineer

Olga Kotova

ERK1/2 mediates insulin stimulation of Na,K-ATPase by phosphorylation of the α-subunit in human skeletal muscle cells


  • Lubna Al-Khalili
  • Olga Kotova
  • Hiroki Tsuchida
  • Ingrid Ehrén
  • Eric Féraille
  • Anna Krook
  • Alexander V. Chibalin

Summary, in English

Insulin stimulates Na+,K+-ATPase activity and induces translocation of Na+,K+-ATPase molecules to the plasma membrane in skeletal muscle. We determined the molecular mechanism by which insulin regulates Na+,K+-ATPase in differentiated primary human skeletal muscle cells (HSMCs). Insulin action on Na +,K+-ATPase was dependent on ERK1/2 in HSMCs. Sequence analysis of Na+,K+-ATPase α-subunits revealed several potential ERK phosphorylation sites. Insulin increased ouabain-sensitive 86Rb+ uptake and [3H]ouabain binding in intact cells. Insulin also increased phosphorylation and plasma membrane content of the Na+,K+-ATPase α 1- and α2-subunits. Insulin-stimulated Na +,K+-ATPase activation, phosphorylation, and translocation of α-subunits to the plasma membrane were abolished by 20 μM PD98059, which is an inhibitor of MEK1/2, an upstream kinase of ERK1/2. Furthermore, inhibitors of phosphatidylinositol 3-kinase (100 wortmannin) and protein kinase C (10 μM GF109203X) had similar effects. Notably, insulin-stimulated ERK1/2 phosphorylation was abolished by wortmannin and GF109203X in HSMCS. Insulin also stimulated phosphorylation of α 1- and α2-subunits on Thr-Pro amino acid motifs, which form specific ERK substrates. Furthermore, recombinant ERK1 and -2 kinases were able to phosphorylate α-subunit of purified human Na +,K+-ATPase in vitro. In conclusion, insulin stimulates Na+,K+-ATPase activity and translocation to plasma membrane in HSMCs via phosphorylation of the α-subunits by ERK1/2 mitogen-activated protein kinase.

Publishing year







Journal of Biological Chemistry





Document type

Journal article


American Society for Biochemistry and Molecular Biology




  • ISSN: 0021-9258