We are investigating the consequences of mitogen-mediated signals to T cells by isolating and characterizing genes that constitute the immediate early transcriptional response to these events. We currently are investigating 2 induced genes that encode integral membrane proteins. Activation-induced changes in cell surface proteins resulting from a primary stimulus play a particularly important role in regulating downstream proliferative and differentiative responses. Important events mediated at the cell surface include the binding of soluble factors and interactions with other cells and extracellular matrix. 276 encodes a protein of approximately 87 kD. The carboxy half of the protein contains seven membrane spanning domains such as those conserved in the class of receptors that bind heterotrimeric G proteins, and an amino-terminal large extracellular domain contains EGF-like repeats and an RGD sequence. The large extracellular domain is co-translationally proteolytically cleaved from the membrane spanning region into an approximately 50 kD protein backbone that remains associated with the cell surface. The structure of the extracellular domain suggests a role in cell/cell or cell/matrix interactions. An interesting possibility is that the extracellular domain of 276 is involved in ligand recognition and serves as a regulatory subunit to the heterotrimeric G protein-coupled receptor. 154 encodes a 158 amino acid type lb membrane protein with a single amino terminal hydrophobic domain and the body of the protein projecting into the cytoplasm. Endogenously-synthesized 154 co-localizes with transferrin receptor in cytoplasmic vesicles, and therefore may be a recycling surface protein or an integral membrane protein involved in vesicle trafficking.
