PTPepsilon has a critical role in signaling transduction pathways and phosphoprotein network topology in red cells

Proteomics. 2008 Nov;8(22):4695-708. doi: 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 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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Algorithms
  • Animals
  • Calcium / analysis
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Clotrimazole / pharmacology
  • Erythrocytes / metabolism*
  • Erythrocytes / ultrastructure
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Metabolic Networks and Pathways*
  • Mice
  • Mice, Knockout
  • Potassium / analysis
  • Protein-Tyrosine Kinases / metabolism
  • Proteomics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4 / metabolism*
  • Signal Transduction* / drug effects
  • Syk Kinase
  • src-Family Kinases / antagonists & inhibitors

Substances

  • Adaptor Proteins, Signal Transducing
  • Calcium Channels
  • Fyb protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse
  • src-Family Kinases
  • Ptpre protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • Clotrimazole
  • Potassium
  • Calcium