Characterized IL-8 signaling pathways. A schematic diagram illustrating the range of signaling pathways that are activated after stimulation of CXCR1 and/or CXCR2 receptors with IL-8. After activation of heterotrimeric small G proteins, IL-8 signaling promotes activation of the primary effectors phosphatidyl-inositol-3-kinase or phospholipase C, promoting the activation of Akt, PKC, calcium mobilization and/or MAPK signaling cascades. These signaling pathways have been shown to promote protein translation (left) and regulate the activity of a range of transcription factors (bottom). Solid gold lines, transcription factors whose activity has been shown to be positively regulated by IL-8 signaling using various reporter assays. In the case of signal transducers and activators of transcription 3 (STAT3) and β-catenin, IL-8 signaling has been shown to promote nuclear translocation of these factors; however, transcriptional activation of either factor remains to be shown. Dashed lines, the putative pathways through which IL-8 signaling regulates transcription factor activity. In addition, IL-8 signaling activates members of the RhoGTPase family and activates a number of nonreceptor tyrosine kinases (e.g., Src family kinases and FAK) that regulate the architecture of the cell cytoskeleton and its interaction with the surrounding extracellular environment (right). http://clincancerres.aacrjournals.org/content/14/21/6735
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