Fyn kinase regulates type II PtdIns 4-kinases in RBL 2H3 cells
Autor: | Naveen Bojjireddy, Gosukonda Subrahmanyam, Ranjeet Kumar Sinha |
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Rok vydání: | 2013 |
Předmět: |
Mast-Cell
Phosphatidylinositol 4-phosphate Clinical Biochemistry Activation Fc Epsilon Ri Receptor Src Family Kinases Proto-Oncogene Proteins c-fyn SH2 domain environment and public health Tyrosine Kinases chemistry.chemical_compound FYN Cell Line Tumor Animals Humans Protein Interaction Domains and Motifs Phosphatidylinositol Phosphorylation Beta-Hexosamindase 1-Phosphatidylinositol 4-Kinase Molecular Biology Sh2 Domain Receptors IgE Affinity Ige Receptor Chemistry Kinase Fc-Epsilon-Ri Phosphatidylinositol 4-Phosphate Rat Splenic Lymphocytes hemic and immune systems Tyrosine phosphorylation Cell Biology General Medicine Key Component beta-N-Acetylhexosaminidases Rats Cell biology Enzyme Activation enzymes and coenzymes (carbohydrates) Rbl-2h3 Cells Phosphatidylinositol 4-Kinase Protein Processing Post-Translational Tyrosine kinase Protein Binding Signal Transduction |
Zdroj: | Molecular and Cellular Biochemistry. 387:63-70 |
ISSN: | 1573-4919 0300-8177 |
DOI: | 10.1007/s11010-013-1871-8 |
Popis: | Type II phosphatidylinositol 4-kinases are implicated in Fc epsilon RI-mediated signaling cascades leading to release of inflammatory molecules. Cross-linking of Fc epsilon RI on RBL 2H3 cells results in protein tyrosine phosphorylation and activation of type II PtdIns 4-kinase activity. Protein tyrosine kinase(s) that phosphorylate type II PtdIns 4-kinase(s) in RBL 2H3 cells remains elusive and is being addressed in this manuscript. Anti-Fyn kinase antibodies co-immunoprecipitated type II PtdIns 4-kinase activity from Fc epsilon RI cross-linked RBL 2H3 cells. In reciprocal assays, His-tagged types II PtdIns 4-kinases were shown to pull down Fyn kinase. Further, anti-Fyn immunoprecipitates were shown to phosphorylate type II PtdIns 4-kinase alpha and beta in in vitro assays. Pull down studies with GST-Fyn-SH2 and GST-Fyn-SH3 domains showed that type II PtdIns 4-kinases associate with Fyn-SH2 domain. Knockdown of Fyn kinase in RBL 2H3 cells abrogated activation of type II PtdIns 4-kinase activity in response to Fc epsilon RI cross-linking and type II PtdIns 4-kinase activity in anti-phosphotyrosine immunoprecipitates. Knockdown of Fyn kinase was also strongly correlated with a reduction in beta-hexosaminidase release in response to Fc epsilon RI cross-linking. These results suggest that type II PtdIns 4-kinases act downstream of Fyn kinase in Fc epsilon RI signaling cascades and are regulated by Fyn kinase. |
Databáze: | OpenAIRE |
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