Phosphorylation of the Na+,K+-ATPase in skeletal muscle: potential mechanism for changes in pump cell-surface abundance and activity.

Abstract

In skeletal muscle, insulin stimulation leads to phosphorylation of Na(+),K(+)-ATPase alpha-subunits on both serine/threonine and tyrosine residues, translocation of Na(+),K(+)-ATPase molecules to the plasma membrane, and increased Na(+),K(+)-ATPase activity. The molecular nature of the tyrosine kinase that phosphorylates Na(+),K(+)-ATPase is not yet identified. In vitro phosphorylation experiments show that the alpha-subunit of Na(+),K(+)-ATPase from skeletal muscle is a substrate for the tyrosine-specific protein kinase c-src. Tyrosine phosphorylation of the alpha-subunits of Na(+),K(+)-ATPase may be an important mechanism for insulin-mediated regulation of Na(+),K(+)-ATPase translocation and activity.