Tyrosine kinases in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

Figure 1

Tyrosine kinases involved in the signal transduction pathways in rheumatoid arthritis. Various tyrosine kinases have important roles in the pathogenesis of RA and these kinases are possible targets for the anti-RA strategy. MAP3K: MAPK kinase kinases, MKK: MAPK kinases, MAPK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinases, Syk: spleen tyrosine kinase, NF-κB: nuclear factor κ-light-chain-enhancer of activated B cells, IKK: IκB kinase, JAK: the Janus kinases, STAT: signal transducers and activators of transcription.