Blobel Carl P, Carpenter Graham, Freeman Matthew
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Department of Medicine, Weil Medical College of Cornell University, New York, NY 10021, USA.
Exp Cell Res. 2009 Feb 15;315(4):671-82. doi: 10.1016/j.yexcr.2008.10.011. Epub 2008 Oct 25.
Proteases are now recognized as having an active role in a variety of processes aside from their recognized metabolic role in protein degradation. Within the ErbB system of ligands and receptors, proteases are known to be necessary for the generation of soluble ligands from transmembrane precursors and for the processing of the ErbB4 receptor, such that its intracellular domain is translocated to the nucleus. There are two protease activities involved in the events: proteases that cleave within the ectodomain of ligand (or receptor) and proteases that cleave the substrate within the transmembrane domain. The former are the ADAM proteases and the latter are the gamma-secretase complex and the rhomboid proteases. This review discusses the roles of each of these protease systems within the ErbB system.
除了在蛋白质降解中公认的代谢作用外，蛋白酶现在还被认为在多种过程中发挥着积极作用。在配体和受体的表皮生长因子受体（ErbB）系统中，已知蛋白酶对于从跨膜前体生成可溶性配体以及处理ErbB4受体是必需的，从而使其细胞内结构域易位至细胞核。这些事件涉及两种蛋白酶活性：在配体（或受体）胞外域内切割的蛋白酶和在跨膜域内切割底物的蛋白酶。前者是解聚素和金属蛋白酶（ADAM），后者是γ-分泌酶复合物和类菱形蛋白酶。本综述讨论了这些蛋白酶系统在ErbB系统中的各自作用。
