In 1991, they found a second tyrosine kinase with this feature. identified that a tyrosine kinase has a recognizable kinase domain and a pseudokinase domain. The discovery of JAKs happened in 1989–1994. 14 Since then, STAT3, STAT4, STAT5a, STAT5b, and STAT6 were found in several laboratories during 1993–1995. 12, 13 Later studies have identified that ISGF3 is comprised of STAT1, STAT2, and IRF9. Thus, Fu proposed a direct effector model for signal transduction induced by IFN-α, which revealed the signal transduction mode of the JAK/STAT signaling pathway. Moreover, a specific IFN-α-induced cytoplasmic tyrosine kinase can phosphorylate and activate ISGF3α. 11 In 1992, Fu reported that 113, 91, and 84 kDa (ISGF3α) proteins of ISGF3 contain conserved SH2 and SH3 domains. 11 In 1990, the transcriptional activator interferon-stimulated gene factor 3 (ISGF3), a transcription factor that responds to IFN-α, was discovered to be composed of multiple interacting polypeptide chains (48, 84, 91, and 113 kDa). The JAK/STAT signaling pathway was first discovered when studying how IFNs lead to the activation of a transcription factor. Finally, we focus on the current market-approved and preclinical medications designed to target this pathway.

10 In this review, we aim to provide updated and comprehensive views of the JAK/STAT signaling pathway at the cellular, molecular, and genomic levels, and elucidate the relationship between JAK/STAT pathway components and human diseases. Currently, many JAK inhibitors have achieved efficacy in many clinical settings, and more medications are currently being studied. 4, 5, 6, 7, 8, 9 Thus, inhibiting the JAK/STAT pathway is promising for treating various diseases. Many papers have reported the importance of this pathway in malignancies and autoimmune diseases. The JAK/STAT signaling pathway has profoundly influenced recent understanding attained of human health and disease. Although STATs can be activated by partially overlapping cytokines, different STATs have nonredundant biological effects. Tyrosine-phosphorylated STATs dimerize and are then transported into the nucleus through the nuclear membrane to regulate specific genes. JAKs are noncovalently associated with cytokine receptors, mediate tyrosine phosphorylation of receptors, and recruit one or more STAT proteins. 2 Loss or mutation of JAK/STAT components is related to many diseases in humans. 1 JAK/STAT-mediated downstream events vary and include hematopoiesis, immune fitness, tissue repair, inflammation, apoptosis, and adipogenesis. More than 50 cytokines and growth factors have been identified in the JAK/STAT signaling pathway, such as hormones, interferons (IFN), interleukins (ILs), and colony-stimulating factors. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is regarded as one of the central communication nodes in the cell function.

Matrix absence management mpn