Janus kinases in immune cell signaling

Immunological Reviews 2009; 228:273-87

This review from 2009 describes the Janus Kinases (JAK) that includes JAK1, JAK2, and JAK3, a subgroup of non-receptor protein tyrosine kinases. This protein family has a diverse range of functions including roles in cell growth, survival, development, and differentiation of a variety of cells, and especially immune and haematopoietic cells. Current knowledge of protein structure, regulatory mechanisms, signalling pathways and intracellular interactions for the JAK family is reviewed. The paper explains that this has allowed new strategies to be developed for the management of malignancies and autoimmune diseases. Eight protein kinase inhibitors (imatinib, gefitinib, dasatinib, sunitinib, erlotinib, nilotinib, lapatinib, and sorafenib) have been approved for use in humans to treat various malignancies. Others like the JAK3 inhibitor tofacitinib are being investigated in other disease areas. JAK2 inhibitors are being developed to treat myeloproliferative disease. [Note: At the time this article was written, tofacitinib was under investigation in phase 2 trials for rheumatoid arthritis, psoriasis, and the prevention of renal transplant rejection]