CD9-mediated activation of the p46 Shc isoform leads to apoptosis in cancer cells
| Autor: | Katsumi Yamamoto, Osamu Kishida, Hitoshi Yoshida, Tatsuya Kiyohara, Yoshiji Miyazaki, Kenji Oritani, Shusaku Tsutsui, Tamana Miyazaki, Yoko Murayama, Yuji Matsuzawa, Shigeki Higashiyama, Yasuhisa Shinomura, Jun-ichiro Miyagawa |
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| Rok vydání: | 2004 |
| Předmět: |
MAPK/ERK pathway
Src Homology 2 Domain-Containing Transforming Protein 1 Time Factors Cell Survival p38 mitogen-activated protein kinases Immunoblotting Apoptosis Biology Transfection p38 Mitogen-Activated Protein Kinases Tetraspanin 29 chemistry.chemical_compound Antigens CD Annexin Cell Line Tumor Neoplasms Cell Adhesion In Situ Nick-End Labeling Humans Immunoprecipitation Protein Isoforms Annexin A5 Coloring Agents Protein kinase A Adaptor Proteins Signal Transducing Cell Proliferation Membrane Glycoproteins Caspase 3 Cell growth Kinase Antibodies Monoclonal Tyrosine phosphorylation Cell Biology Cell biology Enzyme Activation Microscopy Fluorescence Shc Signaling Adaptor Proteins chemistry Caspases Plasmids Thymidine |
| Zdroj: | Journal of Cell Science. 117:3379-3388 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.01201 |
| Popis: | CD9, a member of the tetraspanin family, has been shown to be involved in a range of cellular activities, including migration, proliferation and adhesion, but the molecular mechanisms by which it mediates such events is unclear. Here, we found that anti-CD9 monoclonal antibody ALB6 inhibited cell proliferation, reduced cell viability and induced not only morphological changes specific to apoptosis but also molecular changes, as evidenced by TUNEL and annexin-V staining. For the possible mechanism of ALB6-induced apoptosis, ALB6 activated the c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38 mitogen-activated-protein kinase (MAPK) within 5-15 minutes, as well as caspase-3 within 24-48 hours. It is noteworthy that ALB6 induced tyrosine phosphorylation of the p46 Shc isoform specifically and that the overexpression of its dominant-negative form completely suppressed the ALB6-induced activation of JNK/SAPK, p38 MAPK and caspase-3, resulting in the inhibition of apoptotic cell death. These results suggest that CD9 might regulate apoptosis through the specialized signals in human cancer cell lines. |
| Databáze: | OpenAIRE |
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