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Originally published In Press as doi:10.1074/jbc.M207410200 on September 21, 2002

J. Biol. Chem., Vol. 277, Issue 48, 46364-46373, November 29, 2002
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Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium*

Ruey-Bing YangDagger , Chi Kin Domingos NgDagger , Scott M. WassermanDagger , Steven D. Colman§, Suresh Shenoy§, Fuad Mehraban§, László G. KömüvesDagger , James E. TomlinsonDagger , and James N. TopperDagger

From the Dagger  Department of Cardiovascular Research, Millennium Pharmaceuticals, Inc., South San Francisco, California 94080 and the § Department of Collaborative Research, CuraGen Corporation, New Haven, Connecticut 06511

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.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 650-246-7333; Fax: 650-244-9270; E-mail: Jamie.Topper@mpi.com.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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