The Copper Binding Domain of SPARC Mediates Cell Survival in Vitro via Interaction with Integrin β1 and Activation of Integrin-linked Kinase

摘要: Secreted protein acidic and rich in cysteine (SPARC) is important for the normal growth maintenance of murine lens. SPARC-null animals develop cataracts associated with a derangement lens capsule basement membrane alterations fiber morphology. Cellular stress disregulation apoptotic pathways within epithelial cells (LEC) are linked to cataract formation. To identify molecular targets SPARC that this disorder, we stressed wild-type (WT) LEC by serum deprivation or exposure tunicamycin. enhanced signaling integrin-linked kinase (ILK), serine/threonine known enhance cell survival vitro. In response stress, an ILK-dependent decrease apoptosis was observed WT relative SPARCg-null LEC. Co-immunoprecipitation cross-linking lysates revealed levels SPARC-integrin β1 complex during stress. Competition monoclonal antibodies peptides indicated copper binding domain required SPARC-mediated Inhibiting and/or activity ILK, integrin β1, resulted increased We conclude protects from stress-induced vitro via interaction heterodimers enhances ILK activation pro-survival activity.