Adherens junctions are a specialized class of cell contacts, formed between neighboring cells or between cells and the extracellular matrix. These junctions are highly susceptible to the injury induced by alcohol, aging, carcinogens, tumor promoters or viruses. We have cloned cDNAs for tensin, a novel tyrosine-phosphorylated 200 kD component of adherens junctions, and deduced its complete amino acid sequences. Unexpectedly, it reveals the presence of a SH2 domain, a binding site for phosphotyrosine and shared by a number of signal transduction proteins including nonrecetor tyrosine kinases. We have also cloned and expressed the actin-binding domain of tensin which contains sequences homology with several actin-binding proteins. These findings suggest that by possessing both actin-binding and phosphotyrosine-binding activities and being itself a target for tyrosine kinases, tensin may bridge the signal transduction pathways with the cytoskeleton. We wish to extend these findings and to address the issues of tensin functions. The role of each domains will be studied by genetic, biochemical and cell biological approaches. Various deletion mutants will be created and each domain overexpressed for both functional and structural studies. In addition, other domains of tensin share homology with actin, alpha caterin (a 102 kD cadherin associated protein), beta chains of some lymphokin receptors, or synapsin. Intriguingly, the actin-like sequences is not present in Tetrahymena actin which does not bind tropomyosin. The tensin mutant truncated in this region may help explore whether this is a tropomyosin binding site for tensin. Catenin is present in cell-cell adherens junctions where vinculin and cadherins are abundant. The homologous sequences with tensin are in the vinculin-binding domain of catenin. Deletion mutants in this region may help identify the vinculin-binding domain of tensin. Lymphokin receptors are not tyrosine-kinase receptors but are tyrosine-phosphorylated upon ligand binding. Whether the homologous regions are the association sites with src-family kinases or the tyrosine phosphorylation sites will be studied with deletion mutants. Synapsin binds both actin and synaptic vesicles. The sequence homology suggests that tensin may have additional roles that should also be explored by deletion mutants. Finally, the functions of tensin will further be explored by various knock-out experiments including antisense RNA and homologous recombination.
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