Molecular cloning of delta-4, a new mouse and human notch ligand

Complementary DNAs encoding a previously unidentified mouse Notch ligand an d its human ortholog were isolated. The new Notch Ligand contains a signal sequence, a DSL domain, eight epidermal growth factor-like repeats, a trans membrane domain, and an intracellular region, all of which are characterist ics of members of the Delta protein family. The new protein was therefore d esignated Delta-4, Several previously unidentified sequences in both the ex tracellular and intracellular regions were shown to be conserved among vert ebrate Delta proteins, The tissue distribution of Delta-4 mRNA resembles th at previously described for Notch-4 (Int-3) transcripts. However, in situ h ybridization with mouse lung revealed that Delta-4 mRNA is abundant in squa mous alveolar cells that neighbor endothelial cells; Notch-4 expression is largely restricted to the latter cell type. Soluble forms of the extracellu lar portion of Delta-4 inhibit the apparent proliferation of human aortic e ndothelial cells, but not human pulmonary arterial endothelial cells.