Dikic Ivan, Giordano Silvia
Ludwig Institute for Cancer Research, Husargatan 3, SE-75 124 Uppsala, Sweden.
Curr Opin Cell Biol. 2003 Apr;15(2):128-35. doi: 10.1016/s0955-0674(03)00004-8.
Binding of external factors to cell membrane receptors triggers intracellular signalling pathways that ultimately determine if the cell proliferates, differentiates or undergoes apoptosis. Activated receptors also initiate a cascade of events, called negative receptor signalling, that decreases the amplitude of positive signals and modulates the level of cell stimulation. Recent studies have revealed that negative signalling by receptor tyrosine kinases involves coordinated action of ubiquitin ligases (i.e. Cbl), adaptor proteins (i.e. Grb2 and CIN85), inhibitory molecules (i.e. Sprouty), cytoplasmic kinases (i.e. activated Cdc42-associated kinase) and phosphoinositol metabolites. These inhibitory signals are essential for normal cell functioning, and their deregulation often results in human diseases.
外部因子与细胞膜受体的结合会触发细胞内信号通路，这些信号通路最终决定细胞是增殖、分化还是发生凋亡。活化的受体还会引发一系列称为负性受体信号传导的事件，该过程会降低正性信号的幅度并调节细胞刺激水平。最近的研究表明，受体酪氨酸激酶的负性信号传导涉及泛素连接酶（如Cbl）、衔接蛋白（如Grb2和CIN85）、抑制性分子（如Sprouty）、细胞质激酶（如活化的Cdc42相关激酶）和磷酸肌醇代谢产物的协同作用。这些抑制性信号对于正常细胞功能至关重要，其失调往往会导致人类疾病。
