Disease relevance of TLN1

• Talin is phosphorylated on tyrosine in chicken embryo fibroblasts transformed by Rous sarcoma virus [1].
• A 190 kDa fragment is also generated from talin by the Staphylococcus aureus V-8 proteinase and by trypsin [2].
• Transformation by Y73 also induced elevated levels of phosphotyrosine in talin, whereas transformation by the avian erythroblastosis and Fujinami sarcoma viruses did not [3].
• 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 [4].

High impact information on TLN1

• Here we have investigated the interaction of the purified CSAT antigen with these cytoskeletal components, and we demonstrate an interaction specifically between the CSAT antigen and talin [5].
• An interaction between vinculin and talin [6].
• We have recently discovered a new protein in adhesion plaques which we refer to as talin [6].
• Structural determinants of integrin recognition by talin [7].
• Here we report the crystal structure of the principal integrin binding and activating fragment of talin, alone and in complex with fragments of the beta 3 integrin tail [7].

Chemical compound and disease context of TLN1

• The phosphorylation of talin on tyrosine may be crucial for the expression of the abnormal morphology characteristic of cells transformed by Rous sarcoma virus [1].
• No differences were found in capping efficiency, talin and actin co-localisation or cytoskeletal association of surface-modulated integrin in Rous sarcoma virus (RSV)-transformed cells compared with untransformed counterparts, although differences in the response to cytochalasins were observed [8].

Biological context of TLN1

• We have found that talin phosphorylation increases 3.0-fold upon exposure of chicken embryo fibroblasts to the tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate [9].
• Identification of a talin binding site in the cytoskeletal protein vinculin [10].
• Electron micrographs revealed that the biochemically defined 50-kDa N-terminal talin head domain is composed of two globular subunits, while chemical cross-linking provided evidence that the C-terminal 220-kDa fragment is solely responsible for dimerization [11].
• Living epithelial cells (PtK2) were microinjected during interphase with fluorescent talin [12].
• Vinculin and talin: kinetics of entry and exit from the cytoskeletal pool [13].

Anatomical context of TLN1

• The localization of vinculin and talin in embryonic chicken gizzards indicated that both are primarily cytoplasmic during the first 2 embryonic weeks [14].
• We discuss the possible roles of vinculin and talin in the assembly of membrane-bound dense plaques during the different phases of smooth-muscle development [14].
• Only around days 16-18 does talin apparently become associated with the plasma membrane, this being concomitant with the appearance of distinct myofilament-bound dense plaques [14].
• Immunofluorescence and immunoelectron-microscopic labeling revealed that both proteins are associated with membrane-bound dense plaques in muscle cells; however, the most intense labeling for vinculin was located rather closer to the membrane than that for talin [14].
• Exposure of the cells to tumor promoter did, however, result in a loss of actin and talin-rich cell surface elaborations that resemble focal contact precursor structures [9].

Associations of TLN1 with chemical compounds

• Talin isolated from tumor promoter-treated cells is phosphorylated on serine and threonine residues [9].
• A considerably (3 times) larger fraction of the talin than of the vinculin molecules was found to be phosphorylated on tyrosine [1].
• Phospho amino acid analysis of talin from the infected cells confirmed the presence of phosphotyrosine, in addition to phosphoserine and phosphothreonine [1].
• The cocapping of talin with integrin clusters on CEF could also be observed in the absence of cytochalasins [8].
• Using this antibody we showed by western blot analysis that talin is expressed by RPE cells and is found in the triton-soluble fraction [15].

Physical interactions of TLN1

• The v-src and activated c-src kinases were targeted to adhesion plaques by fusion to the talin-binding sequence of vinculin [16].
• Normal cells also rapidly formed aggregates of integrin and talin after binding to immobilized fibronectin in a manner that was similar to the transformed cells, suggesting that the aggregation process is not dependent upon activity of the pp60v-src tyrosine kinase [17].
• Under these conditions dystrophin bound talin with high affinity (Kd 3.5 nM) [18].
• N-terminal myosin-binding fragment of talin [19].

Co-localisations of TLN1

• Talin was shown to co-localize with integrin and vinculin in the basal region of chick RPE cells isolated from 18-day-old chick embryos [15].

Regulatory relationships of TLN1

• Augmentation of alpha-actinin-induced gelation of actin by talin [20].
• Here, talin-induced perturbations of beta3 NMR resonances were examined to explore integrin activation mechanisms [21].

Other interactions of TLN1

• All of the major components of focal adhesions are also present: alpha-actinin, vinculin, talin, and integrin [22].
• Within 10 min after binding of cells and fibronectin beads at 22 degrees C or 37 degrees C, integrin and talin aggregated at the membrane adjacent to the site of bead attachment [17].
• The interaction of dystrophin with purified talin from chicken gizzard was tested by solid phase immunoassay [18].
• The FERM (four point one, ezrin, radixin, and moesin) domain of talin engages integrins via a novel variant of the canonical phosphotyrosine binding (PTB) domain-NPxY ligand interaction that may be a prototype for FERM domain recognition of transmembrane receptors [7].
• The position of the actin-binding site at the C terminal suggests that talin may work as a crosslinker between myosin and actin [19].

Analytical, diagnostic and therapeutic context of TLN1

• The localization of talin and vinculin in chicken embryo fibroblasts (CEF) during transformation was studied by immunoelectron microscopy [23].
• Talin is an elongated, flexible molecule in high ionic strength buffers, as shown here by rotary shadowing and negative stain electron microscopy [24].
• Radioimmunoassay of tissue extracts and immunolabeling of cultured chick lens cells indicated that the selective presence of talin and of the 135-kD protein in different cell contacts is spatially regulated within individual cells [25].
• This barrel-like geometry, revealed by antibodies to either vinculin or talin, was seen also in teased gizzard strips by confocal laser-scanning microscopy and contrasted with the rib-like surface pattern observed here and previously in other avian and mammalian smooth muscles [26].
• One serum tested by immunoblotting recognized one protein at Mr 215 000 (identical with the value for chicken gizzard talin) and traces of a second at Mr 190 000 (corresponding to a known proteolytic fragment of talin) [27].

References