The Selective Protein Kinase C Inhibitor, Ro-31-8220, Inhibits Mitogen-activated Protein Kinase Phosphatase-1 (MKP-1) Expression, Induces c-Jun Expression, and Activates Jun N-terminal Kinase

• DOI: 10.1074/jbc.271.43.27018
• Publication Date: 2002-07-26T14:51:35Z
• Authors: Jerlyn Beltman; Frank McCormick; Simon J. Cook
• Keywords: c-jun

The role of protein kinase C (PKC) in inflammation, mitogenesis, and differentiation has been deduced part through the use a variety PKC inhibitors. Two widely used inhibitors are structurally related compounds GF109203X Ro-31-8220, both which potently inhibit activity believed to be highly selective. While using Ro-31-8220 address immediate early gene expression, we observed striking differential effects by each these two compounds. Growth factors induce expression products MAP phosphatase-1 (MKP-1), c-Fos c-Jun. inhibits growth factor-stimulated MKP-1 but strongly stimulated c-Jun even absence factors. displays none properties.These data suggest that may have other pharmacological actions addition inhibition. Indeed, stimulates stress-activated kinase, JNK1. Furthermore, apparently activates JNK PKC-independent manner. Neither down-regulation phorbol esters nor inhibition affected ability activate These that, inhibiting PKC, exhibits novel properties independent its PKC. properties.