| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
α-Catenin is an intrinsic component of the cadherin adhesion complex and is a 102 kDa protein with multiple interaction sites, including homodimerization sites, and binding sites for β- and γ-catenin (plakoglobin), α-actinin, and actin. Besides the binding to β- or γ-catenin, it is unknown, however, which interaction is critical for the function of cadherins. By expressing a series of E-cadherin-α-catenin chimeric molecules on leukemia cells (K562), we have identified the region of α-catenin that confers aggregation-inducing activity to nonfunctional tail-less E-cadherin. The region has been mapped to the carboxy-terminal 295 amino acids of α-catenin. The region contains a binding site for F-actin. Consistent with this result, expression in α-catenin deficient cells ( DLD-1/Δα) of a mutant α-catenin molecule consisting of the amino-terminal β-/γ-catenin-binding site and the carboxy-terminal cell adhesion region identified in the above experiments induced E-cadherin-mediated cell aggregation and compaction. Cells expressing E-cadherin chimeric molecules with the homologous carboxy-terminal region of vinculin, which contains the actin-binding site of vinculin, did not, however, aggregate as strongly as ones expressing E-cadherin-α-catenin chimeric molecules.
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