Na,K-ATPase activity modulates Src activation: A role for ATP/ADP ratio
| Autor: | Herman G.P. Swarts, Frans G. M. Russel, Jan B. Koenderink, Natalya U. Fedosova, Karl M. Weigand |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Digoxin
Energy and redox metabolism [NCMLS 4] Swine Biophysics Membrane transport and intracellular motility [NCMLS 5] Kidney Biochemistry Ouabain 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine medicine Animals Humans Phosphorylation Na+/K+-ATPase 030304 developmental biology 0303 health sciences Digitalis-like compound Autophosphorylation Digitalis Glycosides Cell Biology Recombinant Proteins 3. Good health Adenosine Diphosphate Enzyme Activation Adenosine diphosphate src-Family Kinases Membrane transport and intracellular motility Renal disorder [NCMLS 5] chemistry Na K-ATPase ATP–ADP translocase Sodium-Potassium-Exchanging ATPase Adenosine triphosphate 030217 neurology & neurosurgery Src Signal Transduction Membrane transport and intracellular motility Poverty-related infectious diseases [NCMLS 5] medicine.drug Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biochimica et Biophysica Acta. Biomembranes, 1818, 5, pp. 1269-73 Biochimica et Biophysica Acta. Biomembranes, 1818, 1269-73 |
| ISSN: | 0005-2736 |
| Popis: | Contains fulltext : 108799.pdf (Publisher’s version ) (Closed access) Digitalis-like compounds (DLCs), specific inhibitors of Na,K-ATPase, are implicated in cellular signaling. Exposure of cell cultures to ouabain, a well-known DLC, leads to up- or down regulation of various processes and involves activation of Src kinase. Since Na,K-ATPase is the only known target for DLC binding an in vitro experimental setup using highly purified Na,K-ATPase from pig kidney and commercially available recombinant Src was used to investigate the mechanism of coupling between the Na,K-ATPase and Src. Digoxin was used as a representative DLC for inhibition of Na,K-ATPase. The activation of Src kinase was measured as the degree of its autophosphorylation. It was observed that in addition to digoxin, Src activation was dependent on concentrations of other specific ligands of Na,K-ATPase: Na(+), K(+), vanadate, ATP and ADP. The magnitude of the steady-state ATPase activity therefore seemed to affect Src activation. Further experiments with an ATP regenerating system showed that the ATP/ADP ratio determined the extent of Src activation. Thus, our model system which represents the proposed very proximal part of the Na,K-ATPase-Src signaling cascade, shows that Src kinase activity is regulated by both ATP and ADP concentrations and provides no evidence for a direct interaction between Na,K-ATPase and Src. 01 mei 2012 |
| Databáze: | OpenAIRE |
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