Characterization of two patched receptors for the vertebrate hedgehog protein family
Characterization of two patched receptors for the vertebrate hedgehog protein family
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DOI：
10.1073/pnas.95.23.13630
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发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
de Sauvage, FJ
中科院分区：
文献类型：
--
作者：
Carpenter, D;Stone, DM;de Sauvage, FJ
多跨膜蛋白Patched（PTCH）是Sonic Hedgehog（Shh）的受体，Shh是一种涉及胚胎结构形成和肿瘤发生的分泌分子。目前的模型表明Shh与PTCH的结合阻止了PTCH对七跨膜蛋白Smoothened（SMO）的正常抑制。根据该模型，在基底细胞痣综合征中，PTCH突变失活后，SMO信号传导的抑制减轻。最近，PTCH 2，一种与PTCH具有序列同源性的分子，已经被鉴定。为了表征相对于各种Hedgehog蛋白的两种PTCH分子，我们分离了人PTCH 2基因。PTCH和PTCH 2的生物化学分析表明，它们都以相似的亲和力与所有hedgehog家族成员结合，并且它们可以与SMO形成复合物，然而，PTCH和PTCH 2的表达模式并不完全重叠。虽然PTCH在整个小鼠胚胎中表达，但PTCH 2在皮肤和精母细胞中以高水平存在。由于Desert Hedgehog（Dhh）在睾丸中特异性表达并且是生殖细胞发育所需的，因此PTCH 2可能介导其体内活性。PTCH 2的染色体定位将其置于染色体1 p33 -34上，这是一些生殖细胞肿瘤中缺失的区域，增加了PTCH 2可能是Dhh靶细胞中的肿瘤抑制因子的可能性。
The multitransmembrane protein Patched (PTCH) is the receptor for Sonic Hedgehog (Shh), a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis, Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH, According to this model, the inhibition of SMO signaling is relieved after mutational inactivation of PTCH in the basal cell nevus syndrome, Recently, PTCH2, a molecule with sequence homology to PTCH, has been identified. To characterize both PTCH molecules with respect to the various Hedgehog proteins, we have isolated the human PTCH2 gene. Biochemical analysis of PTCH and PTCH2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with SMO, However, the expression patterns of PTCH and PTCH2 do not fully overlap. While PTCH is expressed throughout the mouse embryo, PTCH2 is found at high levels in the skin and in spermatocytes, Because Desert Hedgehog (Dhh) is expressed specifically in the testis and is required for germ cell development, it is likely that PTCH2 mediates its activity in vivo, Chromosomal localization of PTCH2 places it on chromosome 1p33-34, a region deleted in some germ cell tumors, raising the possibility that PTCH2 may be a tumor suppressor in Dhh target cells.