A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities

被引:179
作者
Hahn, H
Christiansen, J
Wicking, C
Zaphiropoulos, PG
Chidambaram, A
Gerrard, B
Vorechovsky, I
Bale, AE
Toftgard, R
Dean, M
Wainwright, B
机构
[1] NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702
[2] NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP,FREDERICK,MD 21702
[3] UNIV QUEENSLAND,CTR CELLULAR & MOLEC BIOL,BRISBANE,QLD 4072,AUSTRALIA
[4] CTR NUTR & TOXICOL,KAROLINSKA INST,DEPT BIOSCI,S-17157 HUDDINGE,SWEDEN
[5] YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520
关键词
D O I
10.1074/jbc.271.21.12125
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Drosophila patched is a segment polarity gene required for the correct patterning of larval segments and imaginal discs during fly development and has a close functional relationship with hedgehog. We have isolated a complete human PATCHED cDNA sequence, which encodes a putative protein of 1296 amino acids, and displays 39% identity and 60% similarity to the Drosophila PATCHED protein, Hydropathy analysis suggests that human PATCHED is an integral membrane protein with a pattern of hydrophobic and hydrophilic stretches nearly identical to that of Drosophila patched, In the developing mouse embryo, patched is initially detected within the ventral neural tube and later in the somites and limb buds, Expression in the limb buds is restricted to the posterior ectoderm surrounding the zone of polarizing activity, The results show that patched is expressed in target tissues of sonic hedgehog, a murine homolog of Drosophila hedgehog suggesting that patched/hedgehog interactions have been conserved during evolution. Human PATCHED maps to human chromosome 9q22.3, the candidate region for the nevoid basal cell carcinoma syndrome. Patched expression is compatible with the congenital defects observed in the nevoid basal cell carcinoma syndrome.
引用
收藏
页码:12125 / 12128
页数:4
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