Inhibition of Basic Secretagogue-Induced Signaling in Mast Cells by Cell Permeable Gαi-Derived Peptides
| Autor: | Tamar Raz, Orly Zavaro, Dana Baram, Ronit Sagi-Eisenberg, Irit Shefler |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cell Membrane Permeability
G protein Molecular Sequence Data Immunology Cell Drug Evaluation Preclinical Connective tissue GTP-Binding Protein alpha Subunits Gi-Go Biology Histamine Release chemistry.chemical_compound medicine Animals p-Methoxy-N-methylphenethylamine Immunology and Allergy Amino Acid Sequence Mast Cells Transducin Phosphorylation Rats Wistar Prostaglandin D2 Integrin beta3 General Medicine Mast cell Peptide Fragments Rats Interleukin 33 medicine.anatomical_structure chemistry Secretagogue GTP-Binding Protein alpha Subunit Gi2 Inflammation Mediators Signal transduction Peptides Protein Processing Post-Translational Signal Transduction |
| Zdroj: | International Archives of Allergy and Immunology. 145:131-140 |
| ISSN: | 1423-0097 1018-2438 |
| DOI: | 10.1159/000108138 |
| Popis: | Background: Basic secretagogues of connective tissue mast cells act as receptor mimetic agents that trigger mast cells by activating G proteins. This leads to simultaneous propagation of two signaling pathways: one that culminates in exocytosis, while the other involves protein tyrosine phosphorylation and leads to release of arachidonic acid metabolites. We have previously shown that introduction of a peptide that comprises the C-terminal end of Gαi3 into permeabilized mast cells inhibits basic secretagogue-induced exocytosis [Aridor et al., Science 1993;262:1569–1572]. We investigated whether cell-permeable peptides, composed of the C-terminus of Gαi3 fused with importation sequences, affect mast cell function. Methods: Following preincubation with the fused peptides, rat peritoneal mast cells were activated by compound 48/80 and analyzed for histamine and prostaglandin D2 release and protein tyrosine phosphorylations. Results: We demonstrate that out of three importation sequences tested only Gαi3 peptide fused with the Kaposi fibroblast growth factor importation sequence (ALL1) inhibited release of histamine. ALL1 as well as a cell-permeable peptide that corresponds to Gαi2 also blocked compound 48/80-stimulated protein tyrosine phosphorylation, though the latter did not block histamine release. ALL1 effect was G protein-specific, as it was incapable of blocking protein tyrosine phosphorylation stimulated by pervanadate. Conclusion: ALL1, a transducible Gαi3-corresponding peptide, blocks the two signaling pathways in mast cells: histamine release and protein tyrosine phosphorylation. Cell permeable peptides that block these two signaling cascades may constitute a novel approach for preventing the onset of the allergic reaction. |
| Databáze: | OpenAIRE |
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