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Differential Regulation of Na,K-ATPase Isozymes by Protein Kinases and Arachidonic Acid

https://doi.org/10.1006/abbi.1998.0904Get rights and content

Abstract

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 inSf-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.

References (66)

  • J.B Lingrel

    J. Biol. Chem.

    (1994)
  • S. Noguchi et al.

    FEBS Lett.

    (1987)
  • A.W. DeTomaso et al.

    J. Biol. Chem.

    (1993)
  • K.A. Eakle et al.

    J. Biol. Chem.

    (1995)
  • G. Fisone et al.

    J. Biol. Chem.

    (1994)
  • P. Beguin et al.

    J. Biol. Chem.

    (1994)
  • J.A. Nathanson et al.

    Neuron

    (1995)
  • J. Orlowski et al.

    J. Biol. Chem.

    (1988)
  • K.J. Sweadner

    Biochim. Biophys. Acta

    (1989)
  • J.B Lingrel et al.

    Prog. Nucleic Acid Res.

    (1990)
  • S.E. Daly et al.

    J. Biol. Chem.

    (1994)
  • S.C. Kozma et al.

    J. Biol. Chem.

    (1993)
  • J.C. Koster et al.

    J. Biol. Chem.

    (1996)
  • A.V. Chibalin et al.

    J. Biol. Chem.

    (1992)
  • J.M. Lowndes et al.

    Biochim. Biophys. Acta

    (1990)
  • M.S. Feschenko et al.

    J. Biol. Chem.

    (1994)
  • M.S. Feschenko et al.

    J. Biol. Chem.

    (1995)
  • J.P. Middleton et al.

    J. Biol. Chem.

    (1993)
  • M.S. Feschenko et al.

    J. Biol. Chem.

    (1997)
  • J.C. Skou et al.

    J. Bioenerg. Biomembr.

    (1992)
  • I.M. Glynn

    The Enzymes of Biological Membranes

    (1985)
  • I.M. Glynn

    J. Physiol.

    (1993)
  • R.W. Mercer

    Int. Rev. Cytol.

    (1993)
  • B. Horowitz et al.

    J. Biol. Chem.

    (1991)
  • S. Lutsenko et al.

    Ann. NY Acad. Sci.

    (1992)
  • G. Blanco et al.

    Biochemistry

    (1995)
  • G. Blanco et al.

    Biochemistry

    (1995)
  • F. Jaisser et al.

    Ann. NY Acad. Sci.

    (1992)
  • A.A. McDonough et al.

    Curr. Opin. Nephrol. Hyper.

    (1993)
  • A.M. Bertorello et al.

    Am. J. Physiol.

    (1993)
  • H.S. Ewart et al.

    Am. J. Physiol.

    (1995)
  • A. Horiuchi et al.

    Mol. Pharmacol.

    (1993)
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    Martonosi, A.

    1

    To whom correspondence should be addressed at Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110. Fax: (314)362-7463. E-mail:[email protected].

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