Differential regulation of Na,K-ATPase isozymes by protein kinases and arachidonic acid.
While several studies have investigated the regulation of the Na, K-ATPase consisting of the alpha1 and beta1 subunits, there is little evidence that intracellular messengers influence the other Na pump isozymes. We studied the effect of different protein kinases and arachidonic acid on the rat Na,K-ATPase isoforms expressed in Sf-9 insect cells. Our results indicate that PKA, PKC, and PKG are able to differentially modify the function of the Na,K-ATPase isozymes. While PKC activation leads to inhibition of all isozymes, PKA activation stimulates the activity of the Na,K-ATPase alpha3 beta1 and decreases that of the alpha1 beta1 and alpha2 beta1 isozymes. In contrast, activation of PKG diminishes the activity of the alpha1 beta1 and alpha3 beta1 isozymes, without altering that of alpha2 beta1. Treatment of cells with arachidonic acid reduced the activities of all the isozymes. The changes in the catalytic capabilities of the Na pump isozymes elicited by PKA and PKC are reflected by changes in the molecular activity of the Na,K-ATPases. One of the mechanisms by which PKA and PKC affect Na pump isozyme activity is through direct phosphorylation of the alpha subunit. In the insect cells, we found a PKA- and PKC-dependent phosphorylation of the alpha1, alpha2 and alpha3 polypeptides. In conclusion, several intracellular messengers are able to modulate the function of the Na,K-ATPase isozymes and some of them in a specific fashion. Because the Na,K-ATPase isozymes have kinetic properties that are unique, this isozyme-specific regulation may be important in adapting Na pump function to the requirements of each cell.
Blanco
G
G
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Sánchez
G
G
Mercer
R W
RW
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002384:Catalysis / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D018411:Spodoptera; D014162:Transfection
D007527:Isoenzymes; D016718:Arachidonic Acid; D011494:Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase