Bredesen Dale E, Mehlen Patrick, Rabizadeh Shahrooz
The Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA.
Physiol Rev. 2004 Apr;84(2):411-30. doi: 10.1152/physrev.00027.2003.
Classical signal transduction is initiated by ligand-receptor interactions. We have described an alternative form of signal transduction that is initiated by the withdrawal of ligands from specific receptors referred to as dependence receptors. This process is widespread, featuring in developmental cell death, carcinogenesis (especially metastasis), neurodegeneration, and possibly subapoptotic events such as neurite retraction and somal atrophy. Initial mechanistic studies of dependence receptors suggest that these receptors form complexes that include specific caspases. Complex formation appears to be a function of ligand-receptor interaction, and dependence receptors appear to exist in at least two conformational states. Complex formation in the absence of ligand leads to caspase activation by a mechanism that in at least some cases is dependent on caspase cleavage of the receptor itself, releasing proapoptotic peptides. Thus these receptors may serve in caspase amplification, and in so doing create cellular states of dependence on their respective ligands.
经典的信号转导由配体-受体相互作用启动。我们描述了一种信号转导的替代形式，它由配体从特定受体（称为依赖受体）上撤离而启动。这个过程很普遍，在发育性细胞死亡、致癌作用（尤其是转移）、神经退行性变以及可能的亚凋亡事件（如神经突回缩和胞体萎缩）中都有体现。对依赖受体的初步机制研究表明，这些受体形成的复合物包含特定的半胱天冬酶。复合物的形成似乎是配体-受体相互作用的一种功能，并且依赖受体似乎至少以两种构象状态存在。在没有配体的情况下形成复合物会通过一种机制导致半胱天冬酶激活，在至少某些情况下，这种机制依赖于受体自身的半胱天冬酶切割，释放促凋亡肽。因此，这些受体可能参与半胱天冬酶的扩增，从而产生对各自配体的细胞依赖状态。
