SOS 1 and R as regulate epithelial tight junction formation in the human airway through EMP 1

The human airway is lined with respiratory epithelial cells, which create a critical barrier through the formation of apical tight junctions. To investigate the molecular mechanisms underlying this process, an RNA i screen for guanine nucleotide exchange factors ( GEF s) was performed in human bronchial epithelial cells (16 HBE ). We report that SOS 1, acting through the Ras/ MEK / ERK pathway, is essential for tight junction formation. Global microarray analysis identifies epithelial membrane protein 1 ( EMP 1), an integral tetraspan membrane protein, as a major transcriptional target. EMP 1 is indispensable for tight junction formation and function in 16 HBE cells and in a human airway basal progenitor‐like cell line ( BC i‐ NS 1.1). Furthermore, EMP 1 is significantly downregulated in human lung cancers. Together, these data identify important roles for SOS 1/Ras and EMP 1 in tight junction assembly during airway morphogenesis.