The T200 family of cell surface glycoproteins is expressed exclusively on hematopoietic cells and different developmentally regulated forms are expressed by individual cell types. This mode of expression has been conserved through evolution implying a fundamental functional role of these molecules. To date, the function of these molecules, which are large (190,000-200,000d), numerous (50,000-100,000 molecules/cell) and partially phosphorylated on serine residues in the 80,000 d cyto plasmic domain, is poorly understood. The goals of the proposed research are to characteristic the mechanism that regulates expression of the different T200 forms, to determine the genetic components responsible for transcription of the T200 gene in hematopoietic cells and to investigate the function of T200. The organization of the genomic regions encoding the cell type-specific T200 sequences will be established and the cap site(s), promoter sequence(s) and upstream regulatory elements identified. An enhancer region responsible for T200 transcription in hematopoietic cells will be sought as well as regulatory trans-acting genes that have been implicated in our present investigations. Functional studies will investigate the properties of T200-negative mutants and transfected cells expressing altered, engineered T200 molecules. Lastly, the analysis of the homing properties of cells with altered T200 expression will be initiated. In vitro cell lines and normal lymphocytes with altered T200 characteristics will be used in these functional studies. From the experiments detailed in this proposal a better understanding of the regulation and function of a major, developmentally regulated hematopoietic cell surface protein will be obtained.
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