THE PROTEIN-KINASE-C INHIBITORS RO-318220 AND GF 109203X ARE EQUALLY POTENT INHIBITORS OF MAPKAP KINASE-1-BETA (RSK-2) AND P70 S6 KINASE

The protein kinase C (PKC) inhibitors Ro 318220 and GP 109203X have be en used in over 350 published studies to investigate the physiological roles of PKC. Here we demonstrate that these inhibitors are not selec tive for PKC isoforms as was previously assumed. Ro 318220 inhibited M APKAP kinase-1 beta (also known as Rsk-2) in vitro (IC50 3 nM) more po tently than it inhibited mixed PKC isoforms (IC50 5 nM), and it also i nhibited p70 S6 kinase (IC50 15 nM). GF 109203X also potently inhibite d MAPKAP kinase-1 beta (IC50 50 nM) and p70 S6 kinase (IC50 100 nM) wi th similar potency to PKC isoforms (IC50 30 nM). The inhibition of MAP KAP kinase-1 beta, p70 S6 kinase, and probably other protein kinases, may explain many of the effects previously attributed to PKC.