Gomes Dawidson A, Rodrigues Michele A, Leite M Fatima, Gomez Marcus V, Varnai Peter, Balla Tamas, Bennett Anton M, Nathanson Michael H
Department of Internal Medicine and Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8019, USA.
J Biol Chem. 2008 Feb 15;283(7):4344-51. doi: 10.1074/jbc.M706550200. Epub 2007 Dec 11.
Hepatocyte growth factor (HGF) is important for cell proliferation, differentiation, and related activities. HGF acts through its receptor c-Met, which activates downstream signaling pathways. HGF binds to c-Met at the plasma membrane, where it is generally believed that c-Met signaling is initiated. Here we report that c-Met rapidly translocates to the nucleus upon stimulation with HGF. Ca(2+) signals that are induced by HGF result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. Translocation of c-Met to the nucleus depends upon the adaptor protein Gab1 and importin beta1, and formation of Ca(2+) signals in turn depends upon this translocation. HGF may exert its particular effects on cells because it bypasses signaling pathways in the cytoplasm to directly activate signaling pathways in the nucleus.
肝细胞生长因子（HGF）对细胞增殖、分化及相关活动至关重要。HGF通过其受体c-Met发挥作用，激活下游信号通路。HGF在质膜处与c-Met结合，一般认为c-Met信号在此处起始。在此我们报告，在用HGF刺激后，c-Met迅速转位至细胞核。HGF诱导的Ca(2+)信号源于细胞核内磷脂酰肌醇4,5-二磷酸的水解及肌醇1,4,5-三磷酸的形成，而非细胞质内。c-Met向细胞核的转位依赖于衔接蛋白Gab1和输入蛋白β1，而Ca(2+)信号的形成反过来又依赖于这种转位。HGF可能对细胞发挥其特定作用，因为它绕过细胞质中的信号通路，直接激活细胞核中的信号通路。
