The JAK (Janus kinase) family members play a role in the transmission of signals from extracellular stimuli across the plasma membrane via the cytoplasm to the nucleus in eukaryotes. The JAK family is comprised of JAK...The JAK (Janus kinase) family members play a role in the transmission of signals from extracellular stimuli across the plasma membrane via the cytoplasm to the nucleus in eukaryotes. The JAK family is comprised of JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), and the complexities underlying their activation and regulation are still being investigated. Here, we review the recent advances of their functions and the underlying mechanism of activation. At the molecular level, recent studies have greatly advanced our knowledge of the structures and organization of the JAK proteins, as well as the mechanism of JAK activation, particularly the role of the pseudokinase domain as a suppressor of the adjacent tyrosine kinase domain’s catalytic activity. We also review recent advances in our understanding of the mechanisms of negative regulation exerted by phosphatase and SH2 (Src homology 2) domain-containing proteins. These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and shed much light on the potential novel strategies for precise treatment of the associated diseases.展开更多
文摘The JAK (Janus kinase) family members play a role in the transmission of signals from extracellular stimuli across the plasma membrane via the cytoplasm to the nucleus in eukaryotes. The JAK family is comprised of JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), and the complexities underlying their activation and regulation are still being investigated. Here, we review the recent advances of their functions and the underlying mechanism of activation. At the molecular level, recent studies have greatly advanced our knowledge of the structures and organization of the JAK proteins, as well as the mechanism of JAK activation, particularly the role of the pseudokinase domain as a suppressor of the adjacent tyrosine kinase domain’s catalytic activity. We also review recent advances in our understanding of the mechanisms of negative regulation exerted by phosphatase and SH2 (Src homology 2) domain-containing proteins. These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and shed much light on the potential novel strategies for precise treatment of the associated diseases.
