A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities
A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities
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DOI：
10.1074/jbc.271.21.12125
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发表时间：
1996-05-24
影响因子：
4.8
通讯作者：
Wainwright, B
中科院分区：
文献类型：
--
作者：
Hahn, H;Christiansen, J;Wainwright, B
果蝇patched基因是果蝇发育过程中幼虫体节和成虫盘正确形成所必需的体节极性基因，与hedgehog基因有着密切的功能关系。我们已经分离了一个完整的人PATCHED cDNA序列，它编码一个1296个氨基酸的推定蛋白，与果蝇PATCHED蛋白具有39%的同源性和60%的相似性。亲水性分析表明，人PATCHED是一个完整的膜蛋白，具有与果蝇PATCHED几乎相同的疏水和亲水延伸模式。patched最初在腹神经管中检测到，随后在体节和肢芽中检测到，肢芽中的表达限于极化活动区周围的后外胚层。结果表明patched在音刺猬的靶组织中表达，果蝇刺猬的一种鼠类同源物，表明补丁/刺猬相互作用在进化过程中是保守的。人类PATCHED定位于人类染色体9q22.3，痣样基底细胞癌综合征的候选区域。斑片状表达与痣样基底细胞癌综合征中观察到的先天性缺陷一致。
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.