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PTPϵ has a critical role in signaling transduction pathways and phosphoprotein network topology in red cells
Author(s) -
De Franceschi Lucia,
Biondani Andrea,
Carta Franco,
Turrini Franco,
Laudanna Carlo,
Deana Renzo,
Brunati Anna Maria,
Turretta Loris,
Iolascon Achille,
Perrotta Silverio,
Elson Ari,
Bulato Cristina,
Brugnara Carlo
Publication year - 2008
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700596
Subject(s) - fyn , syk , signal transduction , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , protein tyrosine phosphatase , src family kinase , biology , lyn , tyrosine phosphorylation , tyrosine kinase , phosphoprotein , kinase , phosphorylation , tyrosine , tyrosine protein kinase csk , crosstalk , chemistry , biochemistry , sh2 domain , physics , optics
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 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.