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 anti- inflammatory 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.
Bhagwat
SS
Signal Pharmaceuticals, 5555 Oberlin Drive, San Diego, CA 92121, USA.
Manning
AM
Hoekstra
MF
Lewis
A