Role of SOCS3 in the crosstalk between Wnt and JAK-STAT pathways
| Autor: | Yu-Jie Shen, 沈裕傑 |
|---|---|
| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 Wnt/β-catenin and JAK/STAT signaling pathways are involved in cellular survival, proliferation, differentiation and apoptosis. Dysregulation of these signaling pathways was implicated in leukemogenesis. Our lab have found β-catenin abnormally accumulated in both acute T cell leukemia Jurkat cell line and homozygous JAK2 V617F mutated HEL cell line. In this study, we further explored that the role of SOCS3 in the crosstalk between WNT and JAK/STAT in HEL and Jurkat cell lines. In previous study, using Janus kinase 2 (JAK2) inhibitor AG490 and JAK-2 knockdown clone, we have demonstrated that inhibition of JAK2 activity significantly reduced Wnt signaling in leukemia cell lines. In the present study, we found that SOCS-3, the downstream gene of JAK-2, was co-precipitated with GSK-3 protein. Therefore, we proposed that SOCS3 can directly bind to GSK-3 that facilitated GSK-3 ubiquitination and degradation, and then indirectly increased the level of β-catenin protein. Our study confirmed that both overexpression of SOCS-3 and addition of BIO, GSK-3 kinase inhibitor can reverse AG490 effects on β-catenin degradation. However, neither knockdown nor overexpression of SOCS-3 did not reduce GSK-3 level, Insteadly, overexprewssion of SOCS-3 decreased the kinase activity of GSK-3, which related to β-catenin expression. The current work demonstrates that GSK-3 kinase activity down-regulates β-catenin under treatment of AG490. Taken together, our work suggests that SOCS-3 can directly interact with GSK-3, which resulted in reduction or/and increase the stability of β-catenin. SOCS3 is an important positive regulator of WNT signaling in erythroleukemia and T cell leukemia. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|