The Sema domain of Met is necessary for receptor dimerization and activation
The Sema domain of Met is necessary for receptor dimerization and activation
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DOI：
10.1016/j.ccr.2004.06.013
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发表时间：
2004-07-01
期刊：
影响因子：
50.3
通讯作者：
Wickramasinghe, D
中科院分区：
文献类型：
--
作者：
Kong-Beltran, M;Stamos, J;Wickramasinghe, D
肝细胞生长因子（HGF）结合细胞外结构域并激活Met受体以诱导有丝分裂、形态发生和运动。Met的胞外结构域由Sema、PSI和四个IPT亚结构域组成。我们研究了这些亚结构域对Met受体二聚化的贡献。我们的观察表明，Sema结构域是必要的二聚化，除了肝细胞生长因子结合。在存在或不存在HGF的情况下，用重组Sema处理Met过表达的肿瘤细胞导致Met介导的信号转导、细胞运动性和迁移降低，其表现方式类似于拮抗性抗Met Fab。这些数据表明，Met的Sema结构域不仅可能代表一种新的抗癌治疗靶点，而且本身也可以作为生物活性剂。
Hepatocyte growth factor (HGF) binds the extracellular domain and activates the Met receptor to induce mitogenesis, morphogenesis, and motility. The extracellular domain of Met is comprised of Sema, PSI, and four IPT subdomains. We investigated the contribution of these subdomains to Met receptor dimerization. Our observations indicate that the Sema domain is necessary for dimerization in addition to HGF binding. Treatment of Met-overexpressing tumor cells with recombinant Sema in the presence or absence of HGF results in decreased Met-mediated signal transduction, cell motility, and migration, behaving in a manner similar to an antagonistic anti-Met Fab. These data suggest that the Sema domain of Met may not only represent a novel anticancer therapeutic target but also acts as a biotherapeutic itself.