Mechanisms of signal transduction activated by sublytic assembly of terminal complement complexes on nucleated cells

The sublytic assembly or C5b-7, C5b-8, and C5b-9, activates membrane phosph olipases through heterotrimeric G proteins and stimulates a variety of cell ular activities including prostanoids, leukotrienes, and cytokines synthesi s. Activation of mitotic signaling through Ras, Raf- 1, ERK 1, and phosphat idylinositol-3 kinase (PI3-K) was induced in B lymphocytes, endothelial, an d smooth muscle cells. PI3-K activation by C5b-9 induced STAT3 phosphorylat ion and translocation from cytoplasm to nucleus. This complex signaling mec hanism is directly involved in many biological functions such as endo- and exocytosis, cell cycle progression, activation of transcription, and protei n synthesis. The key role of this signaling pathway is reflected on cell su rvival and proliferation in acute and chronic inflammation where complement activation is an ubiquitous event.