Abram Clare L, Lowell Clifford A
Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
Front Biosci. 2008 May 1;13:4426-50. doi: 10.2741/3015.
Macrophages are key components of the innate immune response. These cells possess a diverse repertoire of receptors that allow them to respond to a host of external stimuli including cytokines, chemokines, and pathogen-associated molecules. Signals resulting from these stimuli activate a number of macrophage functional responses such as adhesion, migration, phagocytosis, proliferation, survival, cytokine release and production of reactive oxygen and nitrogen species. The cytoplasmic tyrosine kinase Src and its family members (SFKs) have been implicated in many intracellular signaling pathways in macrophages, initiated by a diverse set of receptors ranging from integrins to Toll-like receptors. However, it has been difficult to implicate any given member of the family in any specific pathway. SFKs appear to have overlapping and complementary functions in many pathways. Perhaps the function of these enzymes is to modulate the overall intracellular signaling network in macrophages, rather than operating as exclusive signaling switches for defined pathways. In general, SFKs may function more like rheostats, influencing the amplitude of many pathways.
巨噬细胞是先天性免疫反应的关键组成部分。这些细胞拥有多种受体,使其能够对包括细胞因子、趋化因子和病原体相关分子在内的一系列外部刺激做出反应。这些刺激产生的信号激活多种巨噬细胞功能反应,如黏附、迁移、吞噬作用、增殖、存活、细胞因子释放以及活性氧和氮物质的产生。细胞质酪氨酸激酶Src及其家族成员(Src家族激酶,SFKs)参与了巨噬细胞中的许多细胞内信号通路,这些信号通路由从整合素到Toll样受体等多种受体启动。然而,很难将该家族的任何特定成员与任何特定通路联系起来。Src家族激酶在许多通路中似乎具有重叠和互补的功能。也许这些酶的功能是调节巨噬细胞中的整体细胞内信号网络,而不是作为特定通路的唯一信号开关发挥作用。一般来说,Src家族激酶的作用更像是变阻器,影响许多通路的幅度。