JAKSTAT信号通路.docVIP

Signaling pathways mediating the transduction of information between cells are essential for development, cellular differentiation and homeostasis. Their dysregulation is also frequently associated with human malignancies. The JAK (Janus tyrosine Kinase)-STAT (Signal Transducer and Activator of Transcription) pathway represents one such signaling cascade whose evolutionarily conserved roles include cell proliferation and haematopoiesis. JAK belongs to a family of non-receptor protein tyrosine kinases of approximately 130 kDa, comprising of JAK1, JAK2, JAK3 and TYK2 (non-receptor Protein Tyrosine Kinase-2). STATs are latent cytoplasmic transcription factors that become activated after recruitment to an activated receptor complex. Seven STAT proteins have been identified, STAT1 to 6, including STAT5a and STAT5b, which are encoded by distinct genes. In addition, different isoforms of several STATs have been identified. Evolutionarily conserved in eukaryotic organisms from slime molds to humans, JAK-STAT signaling appears to be an early adaptation to facilitate intercellular communication that has co-evolved with myriad cellular signaling events. This co-evolution has given rise to highly adapted, ligand-specific signaling pathways that control gene expression. In addition, the JAK-STAT signaling pathways are regulated by a vast array of intrinsic and environmental stimuli, which can add plasticity to the response of a cell or tissue (Ref.1 2). Mechanistically, JAK/STAT signaling is relatively simple, with only a few principal components. A variety of ligands including Cytokines, Hormones and Growth factors, and their receptors stimulate the JAK/STAT pathway. Intracellular activation occurs when ligand binding induces the multimerization of receptor subunits. For some ligands, such as Epo (Erythropoietin) and GH (Growth Hormone), the receptor subunits are bound as homodimers while, for others, such as Ifns (Interferons) and ILs (Interleukins), the receptor subunits are