Abstract
Abstract: :
Purpose: To investigate the signaling mechanisms responsible for the promotion of lens cell survival as apoptotic-like processes remove cell organelles and nuclei. Methods: The presence of α6 integrin signaling complexes which could play a role in signaling cell survival were examined by immunoprecipitating α6 integrin and immunoblotting for components of pathways known to be involved in cell survival. Localization of these signaling components in the embryonic lens was determined by immunofluorescence analysis. Results: We have found that the cell survival protein Bcl-2 is highly expressed in the cortical fiber region of day E10 chick embryo lens. We then investigated the hypothesis that upstream regulators of Bcl-2 function, such as JNK, were present in α6 integrin signaling complexes. Our results reveal the presence of an α6 integrin/Src/IGF-1R signaling complex specific to the cortical fiber zone, that has recruited the downstream effectors Shc and JNK, both well-known activators of cell survival pathways. Activated JNK, when translocated to the nucleus, can regulate transcription of Bcl-2. We found activated JNK to be localized to lens cell membranes in the differentiating cortical fiber cells, where it is likely to be associated with the α6 integrin signaling complexes. In this important region for cell survival, where we find Bcl-2 expression to be high, activated JNK is also translocated to the nucleus. Conclusion: Our results suggest that α6 integrin signaling complexes containing Src, IGF-1R, Shc, and JNK signal lens cell survival in the face of intracellular events designed for the loss of cell nuclei and organelles.
Keywords: 580 signal transduction • 323 apoptosis/cell death • 339 cell adhesions/cell junctions