A switch from p130Cas/Crk to Gab1/Crk signaling correlates with anchorage independent growth and JNK activation in cells transformed by the Met receptor oncoprotein
| Autor: | Darren M. Kamikura, Morag Park, Louie Lamorte |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
MAP Kinase Kinase 4 Mice chemistry.chemical_compound Adapter molecule crk Stress Fibers Phosphorylation Tyrosine Oncogene Proteins biology 3T3 Cells Protein-Tyrosine Kinases Proto-Oncogene Proteins c-crk Proto-Oncogene Proteins c-met Vinculin Cell biology Cell Transformation Neoplastic Signal transduction Cell Division Protein Binding Signal Transduction animal structures macromolecular substances Focal adhesion Proto-Oncogene Proteins Cell Adhesion Genetics Animals Phosphotyrosine Molecular Biology Paxillin Adaptor Proteins Signal Transducing Cell Size Mitogen-Activated Protein Kinase Kinases Focal Adhesions Wound Healing Retinoblastoma-Like Protein p130 JNK Mitogen-Activated Protein Kinases Proteins Tyrosine phosphorylation Phosphoproteins Actins Fibronectins Enzyme Activation Cytoskeletal Proteins Crk-Associated Substrate Protein chemistry Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Mutation biology.protein Cancer research |
| Zdroj: | Oncogene. 19:5973-5981 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1203977 |
| Popis: | Cell transformation is associated with anchorage independent growth and morphological changes characterized by reduced adhesion and spreading. The molecular signals that control these events are poorly understood. The Met receptor tyrosine kinase is deregulated in human tumors and an oncogenic derivative of this receptor transforms cells. In this paper we demonstrate that fibroblasts transformed by the Met oncoprotein display decreased cell spreading consistent with the loss of actin stress fibers and vinculin staining focal adhesions. In contrast to control cells, focal adhesion kinase, p130Cas and paxillin are weakly or not detectably tyrosine phosphorylated in Met transformed cells. Moreover, although paxillin and p130Cas associate with the Crk adapter protein in control cells, they fail to associate with Crk in Met transformed cells, yet these cells are motile and capable of wound closure to the same extent as control cells. In Met transformed cells, Crk predominantly associates with the Cbl and Gab1 docking proteins in a tyrosine phosphorylation dependent manner. The coupling of Gab1, but not Cbl, with Crk is retained in cells grown in suspension and enhances JNK activation. We propose that the loss of adhesion dependent signals required for cell cycle progression is compensated through Met induced Gab1/Crk signals. |
| Databáze: | OpenAIRE |
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