RUI: Elucidating the Mechanisms Governing Differential Expression of the Lat Gene

Agnes Scott College, Decatur GA

Investigators

Abstract

The mammalian lat gene encodes an adaptor protein (LAT) that is expressed in only a limited number of cell types, including T cells, mast cells, natural killer cells, and platelets. Tyrosine phosphorylation of the LAT protein following receptor engagement results in its interaction with a variety of downstream signaling molecules, an event essential for proper cellular function. In addition to its cell-type restricted expression pattern, the level of lat mRNA is altered during the process by which T cells are activated to elicit an immune response. Interestingly, it appears that certain signal transduction pathways in T cells stimulate lat gene expression whereas others have an inhibitory effect. The objective of this research is to initiate a comprehensive study into the various molecular processes responsible for differential expression of the lat gene. This objective will be accomplished by the following means: (1) identification of the DNA elements comprising the proximal lat promoter; (2) characterization of the proteins that interact with these defined DNA elements and a determination of their functional relevance in controlling lat gene expression; (3) investigation into the role of the proximal lat promoter in the genes' cell-type specific expression and its differential expression during T cell activation; and (4) examination of the contribution of RNA stability and the role of distal control regions to the regulation of lat gene expression. Studies of the regulation of the lat gene will not only provide important information concerning the molecular mechanisms controlling its expression but in addition will contribute to the establishment of general principles of gene regulation which will be applicable to other genes in a variety of living organisms. This research will be conducted as a collaboration between the principal investigator and undergraduate students at Agnes Scott College, a four-year liberal arts institution for women.