PTPϵ has a critical role in signaling transduction pathways and phosphoprotein network topology in red cells
- 7 November 2008
- journal article
- cell biology
- Published by Wiley in Proteomics
- Vol. 8 (22), 4695-4708
- https://doi.org/10.1002/pmic.200700596
Abstract
Protein tyrosine phosphatases (PTPs) are crucial components of cellular signal transduction pathways. Here, we report that red blood cells (RBCs) from mice lacking PTPϵ (Ptpre−/−) exhibit (i) abnormal morphology; (ii) increased Ca2+‐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.Keywords
This publication has 73 references indexed in Scilit:
- Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeletonBlood, 2006
- Mitogenic modulation of Ca2+‐activated K+ channels in proliferating A7r5 vascular smooth muscle cellsBritish Journal of Pharmacology, 2006
- BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological NetworksBioinformatics, 2005
- Network biology: understanding the cell's functional organizationNature Reviews Genetics, 2004
- Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction NetworksGenome Research, 2003
- Tyrosine Phosphatase-ε Activates Src and Supports the Transformed Phenotype of Neu-induced Mammary Tumor CellsJournal of Biological Chemistry, 2003
- Ca2+ promotes erythrocyte band 3 tyrosine phosphorylation via dissociation of phosphotyrosine phosphatase from band 3Biochemical Journal, 2002
- Functional Abnormalities in Protein Tyrosine Phosphatase ε-Deficient MacrophagesBiochemical and Biophysical Research Communications, 2001
- Emergent Properties of Networks of Biological Signaling PathwaysScience, 1999
- Vanadium increases selective K+-permeability in human erythrocytesToxicology, 1981