Roles of paxillin phosphorylation in IL-3 withdrawal-induced Ba/F3 cell apoptosis
| Autor: | Ae Sun Nah, Kee Oh Chay |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
0301 basic medicine Cell Amino Acid Motifs Apoptosis macromolecular substances environment and public health 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice Annexin Cell Line Tumor Genetics medicine Animals Phosphorylation Molecular Biology Paxillin B-Lymphocytes biology Tyrosine phosphorylation Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology medicine.anatomical_structure chemistry Cell culture biology.protein Interleukin-3 Signal transduction 010606 plant biology & botany |
| Zdroj: | Genesgenomics. 41(2) |
| ISSN: | 2092-9293 |
| Popis: | Ba/F3, a mouse pro-B cell line, is dependent on IL-3 for its survival and proliferation. IL-3 withdrawal causes cells to round, stop in G1 phase, then undergo apoptosis. Additionally, IL-3 is known to induce tyrosine phosphorylation of paxillin, a scaffold and signaling protein. We previously determined that overexpression of paxillin prohibited Ba/F3 cell apoptosis induced by IL-3 withdrawal. Address whether phosphorylation is essential for the anti-apoptotic effect of overexpressed paxillin. Mutations were introduced into paxillin cDNA at five phosphorylation sites—Y31F, Y40F, Y118F, Y181F, S273A, or S273D. After overexpression of paxillin mutants in Ba/F3 cells, the apoptotic proportions of cell populations were measured by an annexin V conjugation assay while cells were undergoing IL-3 withdrawal. The anti-apoptotic effect of paxillin overexpression was abolished by site-directed mutagenesis replacing Y31, Y40, Y118, and Y181 with phenylalanine, and S273 with aspartic acid. In contrast, the mutation replacing S273 with alanine had no effect on the anti-apoptotic effect. The above results suggest that paxillin-mediated phosphorylation at Y31, Y40, Y118, and Y181 is essential for the anti-apoptotic effect of paxillin overexpression in Ba/F3 cells and contributes to the cell survival signaling pathway triggered by IL-3. Conversely, phosphorylation at S273 is involved in the negative regulation of the anti-apoptotic action of overexpressed paxillin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink