Mainiero F, Gismondi A, Soriani A, Cippitelli M, Palmieri G, Jacobelli J, Piccoli M, Frati L, Santoni A
Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome "La Sapienza", 00161 Rome, Italy.
J Exp Med. 1998 Oct 5;188(7):1267-75. doi: 10.1084/jem.188.7.1267.
Recent evidence indicates that integrin engagement results in the activation of biochemical signaling events important for regulating different cell functions, such as migration, adhesion, proliferation, differentiation, apoptosis, and specific gene expression. Here, we report that beta1 integrin ligation on human natural killer (NK) cells results in the activation of Ras/mitogen-activated protein kinase pathways. Formation of Shc-growth factor receptor-bound protein 2 (Grb2) and Shc-proline-rich tyrosine kinase 2-Grb2 complexes are the receptor-proximal events accompanying the beta1 integrin-mediated Ras activation. In addition, we demonstrate that ligation of beta1 integrins results in the stimulation of interferon gamma (IFN-gamma) production, which is under the control of extracellular signal-regulated kinase 2 activation. Overall, our data indicate that beta1 integrins, by delivering signals capable of triggering IFN-gamma production, may function as NK-activating receptors.
最近的证据表明，整合素的结合会导致对调节不同细胞功能（如迁移、黏附、增殖、分化、凋亡和特定基因表达）至关重要的生化信号事件的激活。在此，我们报告人类自然杀伤（NK）细胞上的β1整合素连接会导致Ras/丝裂原活化蛋白激酶途径的激活。Shc-生长因子受体结合蛋白2（Grb2）和Shc-富含脯氨酸的酪氨酸激酶2-Grb2复合物的形成是伴随β1整合素介导的Ras激活的受体近端事件。此外，我们证明β1整合素的连接会导致干扰素γ（IFN-γ）产生的刺激，这受细胞外信号调节激酶2激活的控制。总体而言，我们的数据表明，β1整合素通过传递能够触发IFN-γ产生的信号，可能作为NK激活受体发挥作用。
