| Tsai MT, Cheng CJ |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=4.371 ------>paper_class3=2 ------>paper_class2=1 ------>vol=422 ------>confirm_bywho=jschu ------>insert_bywho=cjcheng ------>Jurnal_Rank=23.9 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=29 ------>paper_class2Letter=None ------>page2=128 ------>medlineContent= ------>unit=E0102 ------>insert_date=20090904 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=0264-6021 ------>authors_c= ------>score=500 ------>journal_name=Biochem J. ------>paper_name=Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans. ------>confirm_date=20090904 ------>tch_id=087010 ------>pmid=19480626 ------>page1=119 ------>fullAbstract=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 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 in HH-related biology and pathology, such as during organ development and tumour progression. ------>tmu_sno=None ------>sno=22155 ------>authors2= ------>authors3=Lin YC ------>authors4=Chen CC ------>authors5=Wu AR ------>authors6=Wu MT, Hsu CC, Yang RB. ------>authors6_c= ------>authors=Tsai MT, Cheng CJ ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans. ------>language=1 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=1 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=7 |