Molecular Cloning of Delta-4, a New Mouse and Human Notch Ligand

• Published in: Journal of biochemistry (Tokyo) Vol. 129; no. 1; pp. 27 - 34
• Main Authors: Yoneya, Takashi, Tahara, Tomoyuki, Nagao, Kenji, Yamada, Yoko, Yamamoto, Terumi, Osawa, Masatake, Miyatani, Seiji, Nishikawa, Mitsuo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.01.2001
• Subjects: Amino Acid Sequence; Animals; Blood Proteins - chemistry; Blood Proteins - classification; Blood Proteins - genetics; Blood Proteins - pharmacology; Cell Division - drug effects; Cloning, Molecular; consensus sequence; Delta; DNA, Complementary - analysis; endothelial cells; Endothelium - cytology; Endothelium - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Growth Substances - chemistry; Growth Substances - classification; Growth Substances - genetics; Growth Substances - pharmacology; Humans; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Mice; Molecular Sequence Data; Notch; Phylogeny; Proto-Oncogene Proteins - chemistry; Receptor, Notch4; Receptors, Cell Surface; Receptors, Notch; Sequence Analysis, Protein; Sequence Homology, Amino Acid; Solubility
• ISSN: 0021-924X
• DOI: 10.1093/oxfordjournals.jbchem.a002832

Complementary DNAs encoding a previously unidentified mouse Notch ligand and its human ortholog were isolated. The new Notch ligand contains a signal sequence, a DSL domain, eight epidermal growth factor-like repeats, a transmembrane domain, and an intracellular region, all of which are characteristics of members of the Delta protein family. The new protein was therefore designated Delta-4. Several previously unidentified sequences in both the extracellular and intracellular regions were shown to be conserved among vertebrate Delta proteins. The tissue distribution of Delta-4 mRNA resembles that previously described for Notch-4 (Int-3) transcripts. However, in situ hybridization with mouse lung revealed that Delta-4 mRNA is abundant in squamous alveolar cells that neighbor endothelial cells;Notch-4 expression is largely restricted to the latter cell type. Soluble forms of the extracellular portion of Delta-4 inhibit the apparent proliferation of human aortic endothelial cells, but not human pulmonary arterial endothelial cells.