Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE

Cheng Fen Tu, Yu Ting Yan, Szu Yao Wu, Bambang Djoko, Ming Tzu Tsai, Chien Jui Cheng, Ruey Bing Yang

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

SCUBE1 (signal peptide-CUB-EGF domain-containing protein 1) is a novel, secreted, cell surface glycoprotein expressed during early embryogenesis and found in platelet and endothelial cells. This protein is composed of an N-terminal signal peptide sequence followed by nine tandemly arranged epidermal growth factor (EGF)-like repeats, a spacer region, three cysteine-rich repeat motifs, and one CUB domain at the C terminus. However, little is known about its domain and biological function. Here, we generated a comprehensive panel of domain deletion constructs and a new genetic mouse model with targeted disruption of Scube1 (Scube1Δcub/Δcub) to investigate the domain function and biological significance. A number of cell-based assays were utilized to define the critical role of the spacer region for membrane association and establish that the EGF-like repeats 7-9 are sufficient for the formation of SCUBE1-mediated homophilic adhesions in a calcium-dependent fashion. Biochemical and molecular analyses showed that the C-terminal cysteine-rich motifs and CUB domain could directly bind and antagonize the bone morphogenetic protein activity. Furthermore, genetic ablation of this C-terminal region resulted in brain malformation in the Scube1 Δcub/Δcub embryos. Together, our results support the dual roles of SCUBE1 on brain morphogenesis and cell-cell adhesions through its distinct domain function.

Original languageEnglish
Pages (from-to)12478-12488
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number18
DOIs
Publication statusPublished - May 2 2008

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Functional analysis
Endothelial cells
Platelets
Epidermal Growth Factor
Membrane Proteins
Blood Platelets
Endothelial Cells
Protein Sorting Signals
Cysteine
Brain
Bone Morphogenetic Proteins
Genetic Models
Cell adhesion
Membrane Glycoproteins
Ablation
Morphogenesis
Cell Adhesion
Embryonic Development
Assays
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE. / Tu, Cheng Fen; Yan, Yu Ting; Wu, Szu Yao; Djoko, Bambang; Tsai, Ming Tzu; Cheng, Chien Jui; Yang, Ruey Bing.

In: Journal of Biological Chemistry, Vol. 283, No. 18, 02.05.2008, p. 12478-12488.

Research output: Contribution to journalArticle

Tu, Cheng Fen ; Yan, Yu Ting ; Wu, Szu Yao ; Djoko, Bambang ; Tsai, Ming Tzu ; Cheng, Chien Jui ; Yang, Ruey Bing. / Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 18. pp. 12478-12488.
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