A Role for CD148 in the control of cell growth and Cell-cell interactions

A variety of signal transduction events are controlled by the opposing, balanced activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Until recently scientists have focused on PTKs, but recent findings have recognized that PTPs play specific and active roles in the regulation of many physiological processes. CD148 is a receptor tyrosine phosphatase with a large extracellular domain and a single catalytic domain. It is expressed on a wide variety of cell types including fibroblasts, endothelial cells, and hematopoietic cells. A number of studies have addressed the role of CD148 in the regulation of cell growth and differentiation using fibroblasts or tumor cell lines. In cultured cells with epithelioid morphology CD148 transcript levels are dramatically upregulated as culture density increases. Although CD148 is expressed on the surface of hemopoietic cells, only a few studies have been published examining the expression of CD148 in human lymphocytes, especially T cells. These reports showed that CD148 plays a role in T cell activation where it participates in the regulation of the T-cell receptor. We have analyzed the possible involvement of CD148 in epithelial growth and cell-cell interactions. Using polarized epithelial cells as a model, we have applied a transcriptional silencing approach based on lentiviral-mediated RNA interference. We show that CD148 expression is required for epithelial cell growth control and proper assembly of epithelial sheets.