Gene-regulating protein kinases as important anti-inflammatory targets

Protein phosphorylation is a key cellular regulatory mechanism. Protein kinases and phosphatases regulate cell-cycle progression, transcription, translation, protein sorting and cell adhesion events that are critical to the inflammatory process. Two of the best-characterized immunosuppressants, cyclosporin and rapamycin, are also effective anti-inflammatory drugs. They act directly on protein phosphorylation and, as such, validate the concept that small-molecule modulators of phosphorylation cascades possess antiinflammatory properties. The authors describe studies that outline progress in defining specific protein kinase signal-transduction cascades, the key drug discovery targets in these cascades and progress towards developing selective agents that have potential in treating numerous inflammatory diseases.