PUBLICATION
Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans
- Authors
- Tsai, M.T., Cheng, C.J., Lin, Y.C., Chen, C.C., Wu, A.R., Wu, M.T., Hsu, C.C., and Yang, R.B.
- ID
- ZDB-PUB-090616-4
- Date
- 2009
- Source
- The Biochemical journal 422(1): 119-128 (Journal)
- Registered Authors
- Yang, Ruey-Bing (Ray)
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Caveolin 1/metabolism
- DNA, Complementary/isolation & purification
- Extracellular Matrix Proteins/chemistry
- Glycosylation
- Hedgehog Proteins/metabolism
- Humans
- Membrane Glycoproteins/isolation & purification*
- Membrane Microdomains/metabolism
- Membrane Proteins/chemistry
- Membrane Proteins/isolation & purification*
- Mice
- Molecular Sequence Data
- NIH 3T3 Cells
- Open Reading Frames/genetics
- Protein Binding
- Protein Structure, Tertiary
- Protein Transport
- Receptors, Cell Surface/metabolism
- Repetitive Sequences, Amino Acid
- Sequence Alignment
- Signal Transduction
- Zebrafish Proteins/chemistry
- PubMed
- 19480626 Full text @ Biochem. J.
Citation
Tsai, M.T., Cheng, C.J., Lin, Y.C., Chen, C.C., Wu, A.R., Wu, M.T., Hsu, C.C., and Yang, R.B. (2009) Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans. The Biochemical journal. 422(1):119-128.
Abstract
SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2) belongs to an evolutionarily conserved SCUBE protein family, which possesses domain organization characteristic of an N-terminal signal peptide sequence followed by 9 epidermal growth factor (EGF)-like repeats, a spacer region, 3 cystein-rich repeat motifs, and one CUB domain at the C terminus. Despite several genetic analyses suggested that the zebrafish orthologue of the mammalian gene SCUBE2 participates in Hedgehog (HH) signaling, the complete full-length cDNA and biochemical function for mammalian SCUBE2 on HH signaling remains uninvestigated. In this study, we isolated the full-length cDNA and studied the role of human SCUBE2 in the HH signaling cascade. When overexpressed, recombinant human SCUBE2 manifests as a secreted, surface-anchored glycoprotein. Deletion mapping analysis defines the critical role of the spacer region and/or cystein-rich repeats for membrane association. Further biochemical analyses and functional reporter assays demonstrated that human SCUBE2 can specifically interact with Sonic HH (SHH) and SHH receptor Patched-1 (PTCH1), and enhance the SHH signaling activity within the cholesterol-rich raft microdomains of the plasma membranes. Together, our results reveal that human SCUBE2 is a novel, positive component of the HH signal, acting upstream in ligand reception at the plasma membrane. Thus, human SCUBE2 could play important roles in HH-related biology and pathology, such as during organ development and tumor progression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping