Cbl negatively regulates erythropoietin-induced growth and survival signaling through the proteasomal degradation of Src kinase

• Material Type: 博士論文
• Title: Cbl negatively regulates erythropoietin-induced growth and survival signaling through the proteasomal degradation of Src kinase
• Author/Editor: 新谷, 高理
• Author Heading: 新谷, 高理
• Publication Date: 2014-12-24
• Publication Date (W3CDTF): 2014-12-24
• Degree grantor/type: 香川大学
• Date Granted: 2014-12-24
• Date Granted (W3CDTF): 2014-12-24
• Dissertation Number: 甲第599号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第599号
• Text Language Code: eng
• Alias of Author: Shintani, Takamichi
• Subject Heading: Cbl; Erythropoietin; Proteasome; Src; Ubiquitination
• Target Audience: 一般
• Note (General): AbstractWe examined the biological functions of the gene Cbl in erythropoietin (EPO) signaling using Cbl-deficient F-36P human erythroleukemia cells by the introduction of the Cbl siRNA expression vector. Knockdown of Cbl promoted EPO-dependent proliferation and survival of F-36P cells, especially at a low concentration of EPO (0.01 U/mL), similar to serum concentrations of EPO in healthy volunteers (0.005–0.04 U/mL). We found that Src was degraded mainly by the proteasomal pathway because the proteasome inhibitor MG-132 but not the lysosome inhibitor NH4Cl suppressed the EPO-induced degradation of Src in F-36P cells and that knockdown of Cbl inhibited EPO-induced ubiquitination and degradation of Src in F-36P cells. The experiments using the Src inhibitor PP1 and co-expression experiments further confirmed that Cbl and the kinase activity of Src are required for the EPO-induced ubiquitination of Src. In addition, the co-expression experiments and in vitro kinase assay demonstrated that the EPO-induced tyrosine phosphorylation and ubiquitination of Cbl were dependent on the kinase activity of Src but not Jak2. Thus, Cbl negatively regulates EPO signaling mainly through the proteasome-dependent degradation of Src, and the E3 ligase activity of Cbl and its tyrosine phosphorylation are regulated by Src but not Jak2.
• DOI: info:doi/10.1016/j.bcmd.2014.06.005; https://doi.org/info:doi/10.1016/j.bcmd.2014.06.005
• Persistent ID (NDL): info:ndljp/pid/10224392; https://dl.ndl.go.jp/pid/10224392
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2016-12-01T22:39:34+09:00
• Date Created (W3CDTF): 2020-10-27
• Format (IMT): PDF
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• Periodical Title (URI): https://kagawa-u.repo.nii.ac.jp/records/231
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp