STAT

Lipopolysaccharide (LPS) also induces chemokine expression in a Stall-dependent manner, although this may involve the intermediate production of lipopolysaccharide (LPS)-induced IFNs (19,20). In vitro, LPS or LPS in combination with IFN-y induces expression of CXCLlO/IP-10 and CCL12/MCP-5 in murine peritoneal macrophages from wild-type, but not Stall-deficient mice (19,20). Injection of LPS in vivo also leads to the expression of CXCLlO/IP-10 in liver and spleen tissues from wild-type but not Statl-deflcient mice (20). 

Stall is critical in the IFN-induced expression of several chemokines and can cooperate or synergize with NF-KB-activating cytokines, such as TNF-a, to increase inflammatory reactions. Further analysis of genes activated by Stall will allow a greater understanding of the role of Stall in regulating specific types of inflammatory responses. 

In the murine system, Stat4 is activated by IL-12 and IL-23 (21-23). In humans, IFN-a also activates Stat4, but this activation is absent in murine cells (24-27). Mice deficient in Stat4 lack all of the known responses to IL-12 (6,7). Lympho- 

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STAT 3 and 5 are overexpressed and/or overactivated in several human malignancies, such as breast,... 

Roosen, C. B., and Hastie, T. J., Automatic smoothing spline projection pursuit. J. Comput. Graph. Stat., 3, 235 (1994). 

Elias KM, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, O Shea JJ Retinoic acid inhibits Thl7 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 2008 111 1013-1020. 

STAT-3 Signal transducer and activator of transcription-3 VEGFR Vascular endothelial growth factor receptor... 

STAT phosphorylation ensures its binding to the receptor, with subsequent disengagement from the receptor in dimeric form. STAT dimerization is believed to involve intermolecular associations between the SH2 domain of one STAT and phosphotyrosine of its partner. Dimerization appears to be an essential prerequisite for DNA binding. Dimers may consist of two identical STATs, but STAT 1-STAT 2 and STAT 1-STAT 3 heterodimers are also frequently formed in response to certain cytokines. The STAT dimers then translocate to the... 

Estimating equation (7.1) yielded an estimate of p of 0.0054 (f-stat = 3.01). This implies that the overall unweighted mean annual rate of FSS price increase of vaccine products during the period 1993-2002 was 0.54%. During the same period, the mean annual rate of increase of the U.S. Consumer Price Index was 2.44%. Hence this implies that the realESS price (the ratio of the nominal FSS price to the Consumer Price Index) declined at an average annual rate of 1.90%. 

The leptin signal is transduced by a mechanism also used by receptors for interferon and growth factors, the JAIC-STAT system (Fig. 23-34 see Fig. 12-9). The leptin receptor, which has a single transmembrane segment, dimerizes when leptin binds to the extracellular domain of two monomers. Both monomers are phos-phorylated on a Tyr residue of the intracellular domain by a Janus kinase (JAK). The -Tyr residues become docking sites for three proteins that are signal transducers and activators of transcription (STATs 3, 5, and 6, sometimes called fat-STATS). The docked STATs are then phosphorylated on Tyr residues by the... 

Stephanou A, Latchman DS. 2005. Opposing actions of STAT-1 and STAT-3. Growth. Factors. 23 177-182. 

Curcumin is a hydrophobic polyphenol derived from turmeric the rhizome of the herb Curcuma longa. Traditionally, turmeric and other curcuminoids have been used in therapeutic preparations for various ailments in different parts of the world. Numerous therapeutic effects of curcumin/turmeric have been confirmed by modern scientific research. It is a highly pleiotropic molecule that modulates numerous targets, including the activation of transcription factors (e.g., NF-kB, STAT-3, AP-1, NRF-2, PPR-y, HIF-1), receptors (e.g., HER-2, IL-8, CXCR-4), kinases (e.g., EGFR, ERK, JAK, AAPK), cytokines (e.g., TNF, IL, MIP, MCP), enzymes (e.g., MMP, iNOS, GST, ATPase), and... 

STATs play a role in embryonic development, like SMADs. In Dmsophila embryos, STATs seem to have a role in the expression of early genes, like STAT 2 and STAT 3 in mammalian embryos. Defects in a STAT homologue are lethal in the larvae of the fly, and the same is true for mammalian embryos embryos of stat3 knock-out mice die before they ever form mesoderm, and stat2 knock-outs do not reach term... 

Also K. Nakashima, M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisaisune, M. Kawabata, et al. Synergistic signalling in fetal brain by STAT 3-Smad 1 complex bridged by p300. Science, 284, 479-482, 1999. 

Stephanou A. Role of STAT-1 and STAT-3 in ischaemia/reperfusion injury. J Cell Mol Med, 2004 8 519-525. 

Julious, S. A. (2004). Using confidence intervals around individual means to assess statistical significance between two means. Pharma-ceut. Stat. 3 217-222. 

W. S. Cleveland, A model for studying display methods of statistical graphics. J Comp Graphical Stat 3 323-343 (1993). 

Fig. 2. Immunohistochemical detection of STAT-3 and pSTAT-3 in the basal hypothalamus of the mouse. Photomicrographs of 40-p.m coronal slices through the ob/ob mouse brain at the level of the arcuate nucleus and median eminence. Brains were collected 30 min after i.v. injeetion of phosphate buffer (PB) or Axokine (0.1 mg/kg) and adjaeent brain slices were processed for detection of STAT-3 (A,C) or phosphorylated STAT-3 (B,D).

Fig. 3. Assessment of signaling in peripheral tissue after systemic administration of Axokine . The left hand group of panels show Western Blot analysis for phosphorylated STAT-3 (upper panel) and STAT-3 (lower panel) in muscle (A), liver (B) and adipose (C) tissues from normal mice 30 min after i.p. injection of Axokine (0.1-1.0 mg/kg), IL-6 (1 mg/kg) or Vehicle. The right hand group of panels shows Northern Blot analysis of mRNA for SOCS-3 (upper panel) in muscle (D), liver (E) and adipose (F) tissues from normal mice 30 or 120 min after i.p. injection of Axokine (0.1-1.0 mg/kg), IL-6 (1 mg/kg) or vehicle.

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