Epidermal growth factor modulates tyrosine phosphorylation of a novel tensin family member, tensin3.
Here, we report the identification of a new tensin family member, tensin3, and its role in epidermal growth factor (EGF) signaling pathway. Human tensin3 cDNA encodes a 1445 amino acid sequence that shares extensive homology with tensin1, tensin2, and COOH-terminal tensin-like protein. Tensin3 is expressed in various tissues and in ... different cell types such as endothelia, epithelia, and fibroblasts. The potential role of tensin3 in EGF-induced signaling pathway is explored. EGF induces tyrosine phosphorylation of tensin3 in MDA-MB-468 cells in a time- and dose-dependent manner, but it is independent of an intact actin cytoskeleton or phosphatidylinositol 3-kinase. Activation of EGF receptor is necessary but not sufficient for tyrosine phosphorylation of tensin3. It also requires Src family kinase activities. Furthermore, tensin3 forms a complex with focal adhesion kinase and p130Cas in MDA-MB-468 cells. Addition of EGF to the cells induces dephosphorylation of these two molecules, leads to disassociation of the tensin3-focal adhesion kinase-p130Cas complex, and enhances the interaction between tensin3 and EGF receptor. Our results demonstrate that tensin3 may function as a platform for the disassembly of EGF-related signaling complexes at focal adhesions.
Mesh Terms:
Actins, Amino Acid Sequence, Cell Line, Tumor, Cloning, Molecular, Crk-Associated Substrate Protein, DNA, Complementary, Epidermal Growth Factor, ErbB Receptors, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Gene Expression Profiling, Humans, Microfilament Proteins, Molecular Sequence Data, Phosphatidylinositol 3-Kinases, Phosphorylation, Phosphotyrosine, Protein Binding, Protein-Tyrosine Kinases, Proteins, Retinoblastoma-Like Protein p130, Sequence Analysis, Protein, Tensins, src-Family Kinases
Actins, Amino Acid Sequence, Cell Line, Tumor, Cloning, Molecular, Crk-Associated Substrate Protein, DNA, Complementary, Epidermal Growth Factor, ErbB Receptors, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Gene Expression Profiling, Humans, Microfilament Proteins, Molecular Sequence Data, Phosphatidylinositol 3-Kinases, Phosphorylation, Phosphotyrosine, Protein Binding, Protein-Tyrosine Kinases, Proteins, Retinoblastoma-Like Protein p130, Sequence Analysis, Protein, Tensins, src-Family Kinases
Mol. Cancer Res.
Date: Apr. 01, 2004
PubMed ID: 15140944
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