This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The major objective of the proposed research plan is to trace the signal transduction pathways responsible for integrin-mediated upregulation of Bcl-2 transcription and cell survival. I will use cell culture and molecular biology techniques. I hypothesize that integrins mediate cell survival by activating signal transduction pathways that lead to increased Bcl-2 expression. This work has the following specific aims: 1. To investigate the role of known signal transduction proteins in integrin mediated upregulation of bcl-2 expression. 2. To isolate by expression cloning proteins that upregulate bcl-2 transcription (BITs) and determine how they affect integrin-mediated signals. 3. To determine the expression patterns of these BIT proteins. 4. To identify proteins that interact with BITs by yeast two-hybrid analysis. Understanding these pathways will provide the molecular mechanism by which integrins mediate survival signals.
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