Activation of focal adhesion kinase in human lung cancer cells involves multiple and potentially parallel signaling events
Autor: | David J. Sugarbaker, Michael T. Jaklitsch, Gavin J. Gordon, Raphael Bueno, Nishit K. Mukhopadhyay, Chang-Jie Chen |
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Rok vydání: | 2005 |
Předmět: |
Collagen Type IV
Cytochalasin D Lung Neoplasms Integrin Naphthalenes Models Biological Article Focal adhesion chemistry.chemical_compound Cell Line Tumor Cell Adhesion Humans Enzyme Inhibitors Phosphorylation Cell adhesion Cytoskeleton Protein Kinase C Paxillin Protein kinase C Cell Proliferation biology Integrin beta1 Autophosphorylation Cell Biology Protein-Tyrosine Kinases Cell biology Enzyme Activation Calphostin C chemistry Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases biology.protein Tyrosine Molecular Medicine Mitogen-Activated Protein Kinases Signal Transduction |
Zdroj: | Journal of Cellular and Molecular Medicine. 9:387-397 |
ISSN: | 1582-4934 1582-1838 |
Popis: | Integrins are adhesion receptors that transmit signals bidirectionally across the plasma membrane. In our previous report we have shown that the squamous lung cancer cell line, Calu-1, binds to collagen type IV (Coll IV) through beta1-integrin and results in phosphorylation of focal adhesion kinase (FAK) (Ann Thorac Surg 2004; 78:450-457). Considering the critical role of FAK in cell migration, proliferation, and survival, here we investigated potential mechanisms of its activation and regulation in Calu-1 cells. We observed the phosphorylation of Tyr397 of FAK (the autophosphorylation site of FAK) and paxillin, the immediate downstream substrate of FAK following the adhesion of Calu-1 cells to Coll IV. FAK remains phosphorylated during proliferation either on Coll IV or on uncoated plates for 72 h, as determined by peroxivanadate treatment. Exposure of Calu-1 cells with 60 microM genistein, reduces FAK phosphorylation (7.6 fold) and cell proliferation. Extracellular signal regulated kinases (ERKs) were also phosphorylated after Coll IV attachment. Disruption of Calu-1 cell cytoskeleton integrity by 1-5 muM Cytochalasin D resulted in the inhibition of cell adhesion (50% to 75%, p |
Databáze: | OpenAIRE |
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