Role of Phosphatidylinositol 4,5-Bisphosphate in Ras/Rac-Induced Disruption of the Cortactin-Actomyosin II Complex and Malignant Transformation
Autor: | Kiyoko Fukami, Richard J. Simpson, Takeshi Watanabe, Cai Huang, Hiroshi Maruta, Tadaomi Takenawa, C. Chandra Kumar, Hong S. He, Xi Zhan, Ed Schuuring |
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Rok vydání: | 1998 |
Předmět: |
Phosphatidylinositol 4
5-Diphosphate Membrane ruffling Molecular Sequence Data Arp2/3 complex macromolecular substances Myosins Oncogene Protein p21(ras) src Homology Domains Mice GTP-Binding Proteins Animals Humans Amino Acid Sequence Cytoskeleton Cell Growth and Development Molecular Biology Adaptor Proteins Signal Transducing Binding Sites biology Microfilament Proteins Actin remodeling 3T3 Cells Actomyosin Blood Proteins Cell Biology Actin cytoskeleton Actins Neoplasm Proteins Rats rac GTP-Binding Proteins Cell biology Rac GTP-Binding Proteins Cell Transformation Neoplastic Cross-Linking Reagents Phenotype Aminoquinolines biology.protein Pyrazoles lipids (amino acids peptides and proteins) Cortactin |
Zdroj: | Scopus-Elsevier |
ISSN: | 1098-5549 |
Popis: | Oncogenic Ras mutants such as v-Ha-Ras cause a rapid rearrangement of actin cytoskeleton during malignant transformation of fibroblasts or epithelial cells. Both PI-3 kinase and Rac are required for Ras-induced malignant transformation and membrane ruffling. However, the signal transduction pathway(s) downstream of Rac that leads to membrane ruffling and other cytoskeletal change(s) as well as the exact biochemical nature of the cytoskeletal change remain unknown. Cortactin/EMS1 is the first identified molecule that is dissociated in a Rac-phosphatidylinositol 4,5-biphosphate (PIP2)-dependent manner from the actin-myosin II complex during Ras-induced malignant transformation; either the PIP2 binder HS1 or the Rac blocker SCH51344 restores the ability of EMS1 to bind the complex and suppresses the oncogenicity of Ras. Furthermore, while PIP2 inhibits the actin-EMS1 interaction, HS1 reverses the PIP2 effect. Thus, we propose that PIP2, an end-product of the oncogenic Ras/PI-3 kinase/Rac pathway, serves as a second messenger in the Ras/Rac-induced disruption of the actin cytoskeleton and discuss the anticancer drug potential of PIP2-binding molecules. |
Databáze: | OpenAIRE |
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