Molecular characterization of human tensin

Abstract

Tensin is a focal-adhesion molecule that binds to actin filaments and interacts with phosphotyrosine-containing proteins. To analyse tensin's function in mammals, we have cloned tensin cDNAs from human and cow. The isolated approx. 7.7-kb human cDNA contains an open reading frame encoding 1735 amino acid residues. The amino acid sequence of human tensin shares 60% identity with chicken tensin, and contains all the structural features described previously in chicken tensin. This includes the actin-binding domains, the Src homology domain 2, and the region similar to a tumour suppressor, PTEN. Two major differences between human and chicken tensin are (i) the lack of the first 54 residues present in chicken tensin, and (ii) the addition of 34- and 38-residue inserts in human and bovine tensin. In addition, our interspecies sequencing data have uncovered the presence of a glutamine/CAG repeat that appears to have expanded in the course of evolution. Northern-blot analysis reveals a 10-kb message in most of the human tissues examined. An additional 9-kb message is detected in heart and skeletal muscles. The molecular mass predicted from the human cDNA is 185 kDa, although both endogenous and recombinant human tensin migrate as 220-kDa proteins on SDS/PAGE. The discrepancy is due to the unusually low electrophoretic mobility of the central region of the tensin polypeptide (residues 306-981). A survey of human prostate and breast cancer cell lines by Western-blot analysis shows a lack of tensin expression in most cancer cell lines, whereas these lines express considerable amounts of focal-adhesion molecules such as talin and focal-adhesion kinase. Finally, tensin is rapidly cleaved by a focal-adhesion protease, calpain II. Incubation of cells with a calpain inhibitor, MDL, prevented tensin cleavage and induced morphological change in these cells, suggesting that cleavage of tensin and other focal-adhesion constituents by calpain disrupts maintenance of normal cell shape.

C1‐TEN is a negative regulator of the Akt/PKB signal transduction pathway and inhibits cell survival, proliferation, and migration

“…Such inhibition of Akt was also seen with PTEN in 293 cells (17). C1-TEN exhibits significant homology to the 215 kDa focal adhesion protein tensin in overall domain organization (2). The markedly altered phenotype displayed by C1-TEN-expressing cells, namely reduced actin staining, may arise from interaction of C1-TEN with cytoskeletal components.…”

Role and significance of focal adhesion proteins in hepatocellular carcinoma

“…Tensin1 is underexpressed in human prostate and breast cancer cell lines. 94 Cten, a COOH-terminal tensin-like member with restricted expression in prostate and placenta is downregulated in prostate cancer. 95 Tensin2 was identified as the second family member of tensin.…”

Gonadotropin‐releasing hormone agonist induces downregulation of tensin 1 in women with endometriosis

“…13,14 Expression of the tensin family of proteins occurs in many organs, including the heart, skeletal muscles, kidneys, lungs, small intestine, liver, colon, prostate, testis, and ovaries. 15 Very low or no expression has been found in the brain, thymus, and circulating leukocytes. 15 In the gynecologic system, TNS1 is involved in implantation 16 and oogenesis, 17 and is expressed in the endometrium.…”