Identification of a novel family of cell-surface proteins expressed in human vascular endothelium.
Vascular endothelial cells (EC) play a key role in a variety of pathophysiologic processes, such as angiogenesis, inflammation, cancer metastasis, and vascular diseases. As part of a strategy to identify all genes expressed in human EC, a full-length cDNA encoding a potential secreted protein harboring 10 epidermal growth factor (EGF)-like domains and one CUB domain at the carboxyl terminus (termed, SCUBE1 for Signal peptide-CUB-EGF-like domain containing protein 1) was identified. SCUBE1 shares homology with several protein families, including members of the fibrillin and Notch families, and the anticoagulant proteins, thrombomodulin and protein C. SCUBE1 mRNA is found in several highly vascularized tissues such as liver, kidney, lung, spleen, and brain and is selectively expressed in EC by in situ hybridization. SCUBE1 is a secreted glycoprotein that can form oligomers and manifests a stable association with the cell surface. A second gene encoding a homologue (designated SCUBE2) was also identified and is expressed in EC as well as other cell types. SCUBE2 is also a cell-surface protein and can form a heteromeric complex with SCUBE1. Both SCUBE1 and SCUBE2 are rapidly down-regulated in EC after interleukin-1beta and tumor necrosis factor-alpha treatment in vitro and after lipopolysaccharide injection in vivo. Thus, SCUBE1 and SCUBE2 define an emerging family of human secreted proteins that are expressed in vascular endothelium and may play important roles in development, inflammation, and thrombosis.
Yang
Ruey-Bing
RB
Department of Cardiovascular Research, Millennium Pharmaceuticals, Inc., South San Francisco, California 94080, USA.
Ng
Chi Kin Domingos
CK
Wasserman
Scott M
SM
Colman
Steven D
SD
Shenoy
Suresh
S
Mehraban
Fuad
F
Komuves
Laszlo G
LG
Tomlinson
James E
JE
Topper
James N
JN
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins; D002460:Cell Line; D017931:DNA Primers; D018076:DNA, Complementary; D004730:Endothelium, Vascular / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; C469998:SCUBE1 protein, human; C469999:SCUBE2 protein, human