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. 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. A mitogen-induced gene cloned from T cells, CD97, encodes a protein of approximately 87 kD. CD97 is constitutively expressed on neutrophils and macrophages and is induced in its expression on T cells and B cells. The carboxy half of the protein demonstrates the seven membrane spanning conserved structure of the class of receptors that bind heterotrimeric G proteins, and a large extracellular domain contains EGF-like repeats and an RGD sequence. CD97 is synthesized as a single polypeptide and proteolytically processed rapidly following its synthesis into extracellular (CD97alpha) and transmembrane (CD97beta) proteins that remain non-covalently associated. The structure of the extracellular domain suggests a role in cell/cell or cell/matrix interactions. Using a purified, soluble form of CD97alpha, we have shown adhesive activity and motility-inducing activity for melanoma cells. The heptahelical structure implies a signal transducing-function. The cellular distribution of CD97 suggests that it may be involved in a function (possibly adhesion) mediated at inflammatory sites. Immunohistochemistry has shown that CD97 is sporadically expressed in lymphocytes in peripheral lymphoid tissues and is expressed at high levels on the majority of leukocytes at inflammatory sites. CD97alpha was found as a stable protein in body fluids from inflammatory sites, implying a potential function for CD97 in a cell-free form.
| Tillinghast, Guy W; Partee, Jason; Albert, Paul et al. (2003) Analysis of genetic stability at the EP300 and CREBBP loci in a panel of cancer cell lines. Genes Chromosomes Cancer 37:121-31 |
