TY - JOUR
T1 - Differential regulation of Na,K-ATpase isozymes by protein kinases and arachidonic acid
AU - Blanco, Gustavo
AU - Sánchez, Gladis
AU - Mercer, Robert W.
N1 - Funding Information:
We thank Drs. Michael Caplan and Douglas Fambrough for kindly supplying the antibodies used in this work. This work was supported by National Institutes of Health grant GM 39746, DK 45181, George O’Brien Kidney and Urological Diseases Center at Washington University School of Medicine and American Heart Association grant 96012080.
PY - 1998/11/15
Y1 - 1998/11/15
N2 - While several studies have investigated the regulation of the Na,K- ATPase consisting of the α1 and β1 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 α3β1 and decreases that of the α1β1 and α2β1 isozymes. In contrast, activation of PKG diminishes the activity of the α1β1 and α3β1 isozymes, without altering that of α2β1. 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 α subunit. In the insect cells, we found a PKA- and PKC-dependent phosphorylation of the α1, α2 and α3 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.
AB - While several studies have investigated the regulation of the Na,K- ATPase consisting of the α1 and β1 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 α3β1 and decreases that of the α1β1 and α2β1 isozymes. In contrast, activation of PKG diminishes the activity of the α1β1 and α3β1 isozymes, without altering that of α2β1. 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 α subunit. In the insect cells, we found a PKA- and PKC-dependent phosphorylation of the α1, α2 and α3 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.
KW - Baculovirus
KW - Isozymes
KW - Na,K-ATPase
KW - Protein kinases
UR - http://www.scopus.com/inward/record.url?scp=0032533595&partnerID=8YFLogxK
U2 - 10.1006/abbi.1998.0904
DO - 10.1006/abbi.1998.0904
M3 - Article
C2 - 9808755
AN - SCOPUS:0032533595
VL - 359
SP - 139
EP - 150
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 2
ER -