The Role of Jak/STAT Signaling in Rheumatoid Arthritis

The biological functions of cytokines, which play an important role in the pathogenesis of rheumatoid arthritis, are achieved by activating signal-transduction cascades that influence cellular activation, proliferation, differentiation, and survival. One of the most often utilized signal-transduction pathways is the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway. Jak is a novel family of cytoplasmic tyrosine kinases pre-associated with cytokine receptors and catalyzing STAT activation by phosphorylation. STATs are latent monomeric proteins that upon activation serve as transcription factors and are present in the cytoplasm of numerous cell types. The mammalian STAT family comprises seven homologous members: STAT-1, -2,-3, -4,-5A, -5B, and -6, encoded by genes located in three chromosomal regions. The role of the STATs in the pathogenesis of rheumatoid arthritis is still being elucidated. In recent years the identification of signal-transduction pathways has suggested new therapeutic targets in rheumatoid arthritis. Modulation of STAT expression represents an alternative therapeutic target to cytokine antagonists, and their inhibition will probably prove more powerful than current treatment strategies (Adv Clin Exp Med 2008, 17, 4, 447-452).