A role for the non-receptor tyrosine kinase ACK1 in TNF-alpha-mediated apoptosis and proliferation in human intestinal epithelial caco-2 cells.
作者： Xinmei Zhao , Chaolan Lv , Shengbo Chen , Fachao Zhi
DOI: 10.1002/CBIN.10875
关键词: Protein kinase B 、 Non-receptor tyrosine kinase 、 PI3K/AKT/mTOR pathway 、 Tumor necrosis factor alpha 、 Cell growth 、 Cell biology 、 Kinase 、 TUNEL assay 、 Cancer research 、 Biology 、 Proto-oncogene tyrosine-protein kinase Src
摘要: The roles of tumor necrosis factor alpha (TNF-alpha) and its mediators in cellular processes related to intestinal diseases remain elusive. In this study, we aimed determine the biological role activated Cdc42-associated kinase 1 (ACK1) TNF-alpha-mediated apoptosis proliferation Caco-2 cells. ACK1 expression was knocked down using ACK1-specific siRNAs, activity disrupted a small molecule inhibitor. Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL) BrdU incorporation assays were used measure cell proliferation, respectively. siRNA pharmacological inhibitor significantly abrogated anti-apoptotic effects Interestingly, TNF-alpha at tyrosine 284 (Tyr284), ErbB family proteins implicated activation ACK1-Tyr284 required for protein B (AKT) activation, signaling mediated through recruiting phosphorylating down-stream adaptor AKT, which likely promoted response TNF-alpha. Moreover, AKT Src enhanced nuclear factor-кB (NF-кB) activity, suggesting correlation between NF-кB Our results demonstrate that plays an important modulating TNF-alpha-induced aberrant apoptosis, part by activation. effectors may hold promise as therapeutic targets prevention treatment gastrointestinal cancers, particular, those induced chronic inflammation.
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