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J. Biochem, 2001, Vol. 129, No. 1 27-34
© 2001 Japanese Biochemical Society

other

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

Takashi Yoneya, Tomoyuki Tahara, Kenji Nagao, Yoko Yamada, Terumi Yamamoto, Masatake Osawa, Seiji Miyatani and Mitsuo Nishikawa1

Pharmaceutical Research Laboratory, Kirin Brewery Co Ltd 3 Miyahara, Takasaki, Gunma 370-1295

1To whom correspondence should be addressed. Tel: +81-27-346-9893, Fax: +81-27-346-1971, E-mail: m-nishikawa{at}kirin.cojp

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.


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