p38 kinase inhibits protein kinase C by blocking autophosphorylation via direct interaction

다국어 초록 (Multilingual Abstract)

Nitric oxide(NO) causes apoptosis of primary culture articular chondrocytes by activating p38 kinase and subsequent inhibition of protein kinase C(PKC)ζ. This study investigated the inhibitory mechanisms of PKC by p38 kinase during NO-induced apoptosis of chondrocytes. Activation of p38 kinase by NO production caused physical association with PKCζ, as determined by co-immunoprecipitation experiments. Direct interaction of p38 kinase with PKC was confirmed by using recombinant proteins of p38 kinase and PKC. The interaction of p38 kinase was specific to PKC among the expressed PKC isoforms, and the interaction was mediated by regulatory domain of PKC. The association of p38 kinase with PKC blocked PKC activity without any effects on p38 kinase activity. In vitro study using recombinant proteins indicated that the interaction of p38 kinase with PKC blocked autophosphorylation of PKC on Ser-113, Ser-186, and Thr-560, which is necessary for the activation of PKC. Taken together, our results provide evidence for a novel mechanism of PKC regulation activation of p38 kinase by NO production in articular chondrocytes inhibits PKC by blocking autophosphorylation via direct interaction.