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- Title
Atypical PKC-ζ and PKC-ι mediate opposing effects on MCF-7 Na<sup>+</sup>/K<sup>+</sup>ATPase activity.
- Authors
Muscella, Antonella; Storelli, Carlo; Marsigliante, Santo
- Abstract
We demonstrated previously that in serum-starved MCF-7 breast cancer cell line, Ang II increased Na+/K+ATPase activity and activated the protein kinase C ζ (PKC-ζ) (Muscella et al., <BIBR>2002</BIBR> J Endocrinol 173:315–323; <BIBR>2003</BIBR> J Cell Physiol 197:61–68.). The aim of the present study was to investigate the modulation of the activity of the Na+/K+ATPase by PKC-ζ in MCF-7 cells. Here, using serum-starved MCF-7 cells, we have demonstrated that the effect of Ang II on the Na+/K+ATPase activity was inhibited by a synthetic myristoylated peptide with sequences based on the endogenous PKC-ζ pseudosubstrate region (ζ-PS) and by high doses of GF109203X, inhibitor of PKCs. When MCF-7 cells, grown in 10% fetal bovine serum (FBS), were stimulated with Ang II a dose- and time-dependent inhibition of the Na+/K+ATPase activity was obtained. Under this growth condition we found that mRNAs for AT1, AT2, and for Na+/K+ATPase α1 and α3 subunits were unchanged; besides both the activity of the Na+/K+ATPase and the level of PKC-ζ also were unaffected by the serum. The atypical PKC-ι level (present in very low abundance in serum-starved MCF-7) was increased and Ang II provoked its translocation from the cytosol to plasma membrane. PKC-ζ was localized to the membrane, and upon Ang II treatment its cellular localization did not change. The Ang II-mediated decrease of the Na+/K+ATPase activity was inhibited by high doses of GF109203X but not by ζ-PS, thus indicating that such effect was not due to PKC-ζ activity. The treatment of cells with PKC-ι antisense oligodeoxynucleotides inhibited the effects of Ang II on the Na+/K+ATPase activity. Additionally, the effect of Ang II on Na+/K+ATPase activity was also blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002, and by the actin depolymerizing agents, cytochalasin D. In conclusion, in MCF-7 cells Ang II modulates the Na+/K+ATPase activity by both atypical PKC-ζ/-ι. The effects of Ang II are opposite depending upon the presence of the serum-sensitive PKC-ι, with the inhibitory effect possibly due to the redistribution of sodium pump from plasma membrane to the inactive intracellular pool. © 2005 Wiley-Liss, Inc.
- Subjects
BREAST cancer; BLOOD proteins; IMMUNE serums; CELL membranes; SERUM
- Publication
Journal of Cellular Physiology, 2005, Vol 205, Issue 2, p278
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.20396