Tartaglia L A, Pennica D, Goeddel D V
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
J Biol Chem. 1993 Sep 5;268(25):18542-8.
To understand the role of the 75-kDa tumor necrosis factor (TNF) receptor in non-lymphoid cells, the cytotoxic signaling and ligand binding activities of the 55-kDa (TNF-R1) and 75-kDa (TNF-R2) TNF receptors were investigated using agonist and antagonist antibodies specific for the two receptor types. This study indicates that although TNF-R2 can significantly reduce the TNF concentration required for cell killing, the mechanism by which this is accomplished is not through the generation of an intracellular signal by TNF-R2. Instead, TNF-R2 regulates the rate of TNF association with TNF-R1, possibly by increasing the local concentration of TNF at the cell surface through rapid ligand association and dissociation. We propose that other cell-surface receptors, such as the low affinity p75 nerve growth factor receptor, may utilize an analogous "ligand passing" mechanism.
为了解75 kDa肿瘤坏死因子（TNF）受体在非淋巴细胞中的作用，我们使用了针对这两种受体类型的激动剂和拮抗剂抗体，研究了55 kDa（TNF-R1）和75 kDa（TNF-R2）TNF受体的细胞毒性信号传导和配体结合活性。这项研究表明，虽然TNF-R2可以显著降低细胞杀伤所需的TNF浓度，但其实现机制并非通过TNF-R2产生细胞内信号。相反，TNF-R2通过快速的配体结合和解离增加细胞表面TNF的局部浓度，从而调节TNF与TNF-R1的结合速率。我们提出，其他细胞表面受体，如低亲和力p75神经生长因子受体，可能利用类似的“配体传递”机制。
