Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans

Ming Tzu Tsai, Chien Jui Cheng, Yuh Charn Lin, Chun Chuan Chen, Ann Ru Wu, Min Tzu Wu, Cheng Chin Hsu, Ruey Bing Yang

研究成果: 雜誌貢獻文章同行評審

51 引文 斯高帕斯(Scopus)

摘要

SCUBE2 [signal peptide, CUB domain, EGF (epidermal growth factor)-like protein 2] belongs to an evolutionarily conserved SCUBE protein family, which possesses domain organization characteristic of an N-terminal signal peptide sequence followed by nine EGF-like repeats, a spacer region, three cysteine-rich repeat motifs, and one CUB domain at the C-terminus. Despite several genetic analyses suggesting that the zebrafish orthologue of the mammalian SCUBE2 gene participates in HH (Hedgehog) signalling, the complete full-length cDNA and biochemical function for mammalian SCUBE2 on HH signalling remains uninvestigated. In the present study, we isolated the full-length cDNA and studied the role of human SCUBE2 in the HH signalling 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 cysteine-rich repeats for membrane association. Further biochemical analyses and functional reporter assays demonstrated that human SCUBE2 can specifically interact with SHH (Sonic Hedgehog) and SHH receptor PTCH1 (Patched-1), and enhance the SHH signalling activity within the cholesterolrich raft microdomains of the plasma membranes. Together, our results reveal that human SCUBE2 is a novel positive component of the HH signal, acting upstream of ligand binding at the plasma membrane. Thus human SCUBE2 could play important roles in HH-related biology and pathology, such as during organ development and tumour progression.

原文英語
頁(從 - 到)119-128
頁數10
期刊Biochemical Journal
422
發行號1
DOIs
出版狀態已發佈 - 八月 15 2009

ASJC Scopus subject areas

  • 生物化學
  • 細胞生物學
  • 分子生物學

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