Signaling by STATs 英文参考文献.docVIP

Available online /content/6/4/159 Review Signaling by STATs Lionel B Ivashkiv and Xiaoyu Hu Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Graduate Program in Immunology, Weill Graduate School of Medical Sciences of Cornell University, New York, New York, USA Corresponding author: Lionel B Ivashkiv, ivashkivl@ Received: 16 Apr 2004 Accepted: 18 May 2004 Published: 21 Jun 2004 Arthritis Res Ther 2004, 6:159-168 (DOI 10.1186/ar1197) ? 2004 BioMed Central Ltd Abstract A variety of cytokines and growth factors use the Janus kinase (Jak)–STAT signaling pathway to transmit extracellular signals to the nucleus. STATs (signal transducers and activators of transcription) are latent cytoplasmic transcription factors. There are seven mammalian STATs and they have critical, nonredundant roles in mediating cellular transcriptional responses to cytokines. The physiological roles of STATs have been elucidated by analysis of mice rendered deficient in STAT genes. STAT activation is regulated and can be modulated in a positive or negative fashion; it can be reprogrammed to drive different cellular responses. Several auto-regulatory and signaling crosstalk mechanisms for regulating Jak–STAT signaling have been described. Understanding and manipulation of the function of STATs will help in the development of therapeutic strategies for diseases that are regulated by cytokines. Keywords: cytokine, inhibition, Jak, signal transduction, STAT Basic Jak–STAT signaling Jaks are protein tyrosine kinases that are pre-associated with membrane-proximal regions (termed box 1 and box 2) of cytokine receptors. It seems that only four mammalian Jaks exist: Jak1, Jak2, Jak3, and Tyk2. Each contains a catalytically active kinase domain and a regulatory pseudo- kinase domain at the carboxy terminus of the protein. The domain responsible for the binding of Jaks to receptors is located at the amino terminus. The bin