Interactions between Important Regulatory Proteins and Human αB Crystallin

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