Interactions between important regulatory proteins and human αB crystallin

Protein pin arrays assessed interactions between alpha B crystallin and 12 regulatory proteins, including EGF, FGF-2, IGF-1, NGF-beta, TGF-beta, VEGF, insulin, beta-catenin, caspase-3, caspase-8, Bcl-2, and Bcl-x(L), which are important in cellular differentiation, proliferation, signaling, cytoskeletal assembly, and apoptosis. FGF-2, NGF-beta, VEGF, insulin, and beta-catenin had strong interactions with human alpha B crystallin peptides, and the alpha B crystallin interactive sequences for these proteins were identified. The seven remaining proteins (EGF, IGF-1, TGF-beta, caspase-3, caspase-8, BCl-2, and Bcl-x(L)) did not interact with alpha B crystallin. The alpha B crystallin sequences that interacted with FGF-2, NGF-beta, VEGF, insulin, and beta-catenin overlapped with sequences that selectively interact with partially unfolded proteins, suggesting a common function for alpha B crystallin in chaperone activity and the regulation of cell growth and differentiation. Chaperone assays conducted with full-length alpha B crystallin and synthetic alpha B crystallin peptides confirmed the ability of alpha B crystallin to protect against the aggregation of FGF-2 and VEGF, suggesting that alpha B crystallin protects these proteins against unfolding and aggregation under conditions of stress. This is the first report in which sequences involved in interactions with regulatory proteins, including FGF-2, NGF-beta, VEGF, insulin, and beta-catenin, were identified in a small heat shock protein.