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.
Cui
Yumin
Y
Center for Tissue Regeneration and Repair, Department of Orthopedic Surgery, University of California-Davis, Sacramento, California 95817, USA.
Liao
Yi-Chun
YC
Lo
Su Hao
SH
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D050719:Crk-Associated Substrate Protein; D018076:DNA, Complementary / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020869:Gene Expression Profiling; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D020539:Sequence Analysis, Protein; D000070876:Tensins; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D018076:DNA, Complementary; D008840:Microfilament Proteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; C000603369:TNS1 protein, human; C000603370:TNS3 protein, human; D000070876:Tensins; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019061:src-Family Kinases