期刊
BIOCHEMICAL JOURNAL
卷 422, 期 -, 页码 119-128出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20090341
关键词
cell-surface protein; CUB domain; epidermal growth factor-like repeat (EGF-like repeat); glycoprotein; signal transduction; Sonic Hedgehog
资金
- Institute of Biomedical Sciences [IBMS-CRC96-P01]
- Academia Sinica [AS-97-FP-L16]
- National Science Council [NSC 97-2752-B-006-003-PAE, NSC 97-2752-B-001-002-PAE, NSC 96-2320-B-038-027, NSC 94-3112-B-001-003, NSC 94-3112-B-001-018-Y]
SCUBE2 [signal peptide, CUB domain, EGF (epidermal growth factor)-like protein 2] belongs to all 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 ill HH (Hedgehog) signalling, the complete full-length cDNA and biochemical function for mammalian SCUBE2 oil HH signalling remains uninvestigated. Ill 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 call specifically interact with SHH (Sonic Hedgehog) and SHH receptor PTCH1 (Patched-1), and enhance the SHH signalling 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 of ligand binding at the plasma membrane. Thus human SCUBE2 could play important roles ill HH-related biology and Pathology, Such as during or-all development and tumour progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据