Ouabain binding to Na+,K+-ATPase relaxes cell attachment and sends a specific signal (NACos) to the nucleus
- PMID: 15216416
- DOI: 10.1007/s00232-004-0670-2
Ouabain binding to Na+,K+-ATPase relaxes cell attachment and sends a specific signal (NACos) to the nucleus
Abstract
Abstract. In previous work we described a "P-->A mechanism" that transduces occupancy of the pump ( P) by ouabain into changes in phosphorylation, stimulation of mitogen-activated protein kinase (MAPK), and endocytosis of cell-cell- and cell-substrate-attaching molecules ( A), thereby causing a release of the cell from the monolayer. In the present work we try to understand the mechanism of this effect; whether, in order to trigger the P-->A mechanism, ouabain should block the pumping activity of Na(+),K(+)-ATPase as pump, or whether it would suffice that the drug occupies this enzyme as a receptor. We assay a series of drugs known to act on the pump, such as ouabain, digoxin, digitoxin, palytoxin, oligomycin, strophanthidin, neothyoside-A, proscillaridin-A, etc. We gauge their ability to block the pump by measuring the K(+) content in the cells, and their ability to detach the cells from the monolayer by determining the amount of protein remaining in the culturing well. None of the drugs tested was able to cause detachment without stopping the pump. Ouabain also enhances phosphorylation, yet pump inhibition and signal transduction do not seem to be intimately associated in a causal chain, but to occur simultaneously. To investigate the response of the site of cell attachment, we analyze the position of beta-catenin by fluorescence confocal microscopy, and find that this adherent junction-associated molecule is sent to the nucleus, where it is known to act as a transcriptional cofactor.
Similar articles
-
Relationship between Na(+),K(+)-ATPase and cell attachment.J Cell Sci. 1999 Dec;112 ( Pt 23):4223-32. doi: 10.1242/jcs.112.23.4223. J Cell Sci. 1999. PMID: 10564641
-
Ouabain Modulates the Adherens Junction in Renal Epithelial Cells.Cell Physiol Biochem. 2019;52(6):1381-1397. doi: 10.33594/000000097. Cell Physiol Biochem. 2019. PMID: 31075189
-
Differential activation of mitogen-activated protein kinases by palytoxin and ouabain, two ligands for the Na+,K+-ATPase.Toxicol Appl Pharmacol. 1998 Aug;151(2):377-84. doi: 10.1006/taap.1998.8471. Toxicol Appl Pharmacol. 1998. PMID: 9707514
-
Ouabain interaction with cardiac Na/K-ATPase reveals that the enzyme can act as a pump and as a signal transducer.Cell Mol Biol (Noisy-le-grand). 2001 Mar;47(2):383-90. Cell Mol Biol (Noisy-le-grand). 2001. PMID: 11357899 Review.
-
Na+,K+-ATPase and hormone ouabain:new roles for an old enzyme and an old inhibitor.Cell Mol Biol (Noisy-le-grand). 2006 Dec 30;52(8):31-40. Cell Mol Biol (Noisy-le-grand). 2006. PMID: 17535734 Review.
Cited by
-
[Na+]i/[K+]i -independent death of ouabain-treated renal epithelial cells is not mediated by Na+,K+ -ATPase internalization and de novo gene expression.Pflugers Arch. 2008 Jan;455(4):711-9. doi: 10.1007/s00424-007-0283-6. Epub 2007 Jul 11. Pflugers Arch. 2008. PMID: 17622553
-
The polarized distribution of Na+,K+-ATPase: role of the interaction between {beta} subunits.Mol Biol Cell. 2010 Jul 1;21(13):2217-25. doi: 10.1091/mbc.e10-01-0081. Epub 2010 May 5. Mol Biol Cell. 2010. PMID: 20444976 Free PMC article.
-
Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease.Am J Physiol Renal Physiol. 2013 Sep 15;305(6):F797-812. doi: 10.1152/ajprenal.00248.2013. Epub 2013 Jun 12. Am J Physiol Renal Physiol. 2013. PMID: 23761677 Free PMC article. Review.
-
Ouabain Accelerates Collective Cell Migration Through a cSrc and ERK1/2 Sensitive Metalloproteinase Activity.J Membr Biol. 2019 Dec;252(6):549-559. doi: 10.1007/s00232-019-00066-5. Epub 2019 Apr 30. J Membr Biol. 2019. PMID: 31041466
-
Digitoxin and its analogs as novel cancer therapeutics.Exp Hematol Oncol. 2012 Apr 5;1(1):4. doi: 10.1186/2162-3619-1-4. Exp Hematol Oncol. 2012. PMID: 23210930 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources