Abstract
Protein tyrosine phosphatases (PTPs) are crucial components of cellular signal transduction pathways. Here, we report that red blood cells (RBCs) from mice lacking PTPepsilon (Ptpre(-/-)) exhibit (i) abnormal morphology; (ii) increased Ca(2+)-activated-K(+) channel activity, which was partially blocked by the Src family kinases (SFKs) inhibitor PP1; and (iii) market perturbation of the RBC membrane tyrosine (Tyr-) phosphoproteome, indicating an alteration of RBC signal transduction pathways. Using the signaling network computational analysis of the Tyr-phosphoproteomic data, we identified seven topological clusters. We studied cluster 1 containing Fyn, SFK, and Syk another tyrosine kinase. In Ptpre(-/-)mouse RBCs, the activity of Fyn was increased while Syk kinase activity was decreased compared to wild-type RBCs, validating the network computational analysis, and indicating a novel signaling pathway, which involves Fyn and Syk in regulation of red cell morphology.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Algorithms
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Animals
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Calcium / analysis
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Calcium Channels / drug effects
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Calcium Channels / metabolism
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Clotrimazole / pharmacology
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Erythrocytes / metabolism*
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Erythrocytes / ultrastructure
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Intracellular Signaling Peptides and Proteins / metabolism
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Metabolic Networks and Pathways*
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Mice
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Mice, Knockout
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Potassium / analysis
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Protein-Tyrosine Kinases / metabolism
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Proteomics
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Receptor-Like Protein Tyrosine Phosphatases, Class 4 / metabolism*
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Signal Transduction* / drug effects
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Syk Kinase
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src-Family Kinases / antagonists & inhibitors
Substances
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Adaptor Proteins, Signal Transducing
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Calcium Channels
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Fyb protein, mouse
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Intracellular Signaling Peptides and Proteins
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse
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src-Family Kinases
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Ptpre protein, mouse
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Receptor-Like Protein Tyrosine Phosphatases, Class 4
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Clotrimazole
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Potassium
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Calcium