Molecular cloning of delta-4, a new mouse and human Notch ligand.
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.
Yoneya
T
T
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Miyahara, Takasaki, Gunma 370-1295, Japan.
Tahara
T
T
Nagao
K
K
Yamada
Y
Y
Yamamoto
T
T
Osawa
M
M
Miyatani
S
S
Nishikawa
M
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006133:Growth Substances / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D018076:DNA, Complementary; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch