Control of erythrocyte metabolism by redox-regulated tyrosine phosphatases and kinases |
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Authors: | P S Low A Kiyatkin Q Li M L Harrison |
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Institution: | (1) Department of Chemistry, Purdue University, 47907 West Lafayette, IN, USA;(2) Departments of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Indiana |
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Abstract: | Summary We wish to elaborate a novel mechanism of metabolic regulation mediated by cytoplasmic tyrosine phosphatases and kinases. Briefly we propose that phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) bind reversibly to the N-terminus of the cytoplasmic domain of band 3. Once the enzymes are bound, they are inhibited; however, upon release they are restored to full activity. We demonstrate that control of enzyme binding and consequently control of substrate flow down the pathway is executed by phosphorylation of Tyr 8 and Tyr 21 within the glycolytic enzyme binding site at the N-terminus of band 3. This phosphorylation results in obstruction of enzyme binding, leading to enzyme activation. Importantly, the tyrosine kinase that phosphorylates band 3 is activated by oxidation, while the tyrosine phosphatase that dephosphorylates band 3 is inhibited by the same redox changes. Consequently, treatment of red cells wih oxidants such as H2O2 and ferricyanide can enhance both tyrosine phosphorylation of the N-terminus of band 3 and glycolysis in a coordinate manner. Because oxidant entry into the cell is not essential, a plasma membrane electron transport pathway is believed to mediate the oxidant's effects. |
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Keywords: | Tyrosine kinase Glycolysis Pentose phosphate pathway Plasma membrane redox shuttle |
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