Interactions between important regulatory proteins and human alphaB crystallin.
Protein pin arrays assessed interactions between alphaB 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-xL, 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 alphaB crystallin peptides, and the alphaB 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-xL) did not interact with alphaB crystallin. The alphaB 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 alphaB crystallin in chaperone activity and the regulation of cell growth and differentiation. Chaperone assays conducted with full-length alphaB crystallin and synthetic alphaB crystallin peptides confirmed the ability of alphaB crystallin to protect against the aggregation of FGF-2 and VEGF, suggesting that alphaB 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.
Ghosh
Joy G
JG
Biomolecular Structure and Design, University of Washington, Seattle, Washington 98195-7420, USA.
Shenoy
Ananth K
AK
Clark
John I
JI
D002454:Cell Differentiation; D049109:Cell Proliferation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D018832:Molecular Chaperones; D020932:Nerve Growth Factor / Q000378:metabolism; D040081:Protein Array Analysis; D011485:Protein Binding; D025941:Protein Interaction Mapping; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism* / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
D007328:Insulin; D018832:Molecular Chaperones; C502240:NGF protein, human; D042461:Vascular Endothelial Growth Factor A; D038203:alpha-Crystallin B Chain; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2; D020932:Nerve Growth Factor