scholarly journals Nuclear Factor of Activated T Cells 1 (NFAT1)-induced Permissive Chromatin Modification Facilitates Nuclear Factor-κB (NF-κB)-mediated Interleukin-9 (IL-9) Transactivation

2012 ◽  
Vol 287 (19) ◽  
pp. 15445-15457 ◽  
Author(s):  
Arijita Jash ◽  
Anupama Sahoo ◽  
Gi-Cheon Kim ◽  
Chang-Suk Chae ◽  
Ji-Sun Hwang ◽  
...  
2004 ◽  
Vol 32 (1) ◽  
pp. 113-115 ◽  
Author(s):  
P. Antony ◽  
J.B. Petro ◽  
G. Carlesso ◽  
N.P. Shinners ◽  
J. Lowe ◽  
...  

Engagement of the B-cell antigen receptor (BCR) induces the activation of various transcription factors, including NFAT (nuclear factor of activated T-cells) and NF-κB (nuclear factor κB), which participate in long-term biological responses such as proliferation, survival and differentiation of B-lymphocytes. We addressed the biochemical basis of this process using the DT40 chicken B-cell lymphoma. We discovered that Bruton's tyrosine kinase (BTK) and phospholipase C-γ2 (PLC-γ2) are required to activate NFAT and NF-κB, and to produce the lipid second messenger diacylglycerol in response to BCR cross-linking. Therefore the functional integrity of the BTK/PLC-γ2/diacylglycerol signalling axis is crucial for BCR-directed activation of both transcription factors NFAT and NF-κB.


2014 ◽  
Vol 42 (6) ◽  
pp. 1484-1489 ◽  
Author(s):  
Pulak R. Nath ◽  
Noah Isakov

Protein kinase Cθ (PKCθ) is a key enzyme in T-lymphocytes where it plays an important role in signal transduction downstream of the activated T-cell receptor (TCR) and the CD28 co-stimulatory receptor. Antigenic stimulation of T-cells triggers PKCθ translocation to the centre of the immunological synapse (IS) at the contact site between antigen-specific T-cells and antigen-presenting cells (APCs). The IS-residing PKCθ phosphorylates and activates effector molecules that transduce signals into distinct subcellular compartments and activate the transcription factors, nuclear factor κB (NF-κB), nuclear factor of activated T-cells (NFAT) and activating protein 1 (AP-1), which are essential for the induction of T-cell-mediated responses. Besides its major biological role in T-cells, PKCθ is expressed in several additional cell types and is involved in a variety of distinct physiological and pathological phenomena. For example, PKCθ is expressed at high levels in platelets where it regulates signal transduction from distinct surface receptors, and is required for optimal platelet activation and aggregation, as well as haemostasis. In addition, PKCθ is involved in physiological processes regulating insulin resistance and susceptibility to obesity, and is expressed at high levels in gastrointestinal stromal tumours (GISTs), although the functional importance of PKCθ in these processes and cell types is not fully clear. The present article briefly reviews selected topics relevant to the biological roles of PKCθ in health and disease.


2004 ◽  
Vol 26 (4) ◽  
pp. 545-558
Author(s):  
Hye‐Young Shin ◽  
Yung‐Sun Song ◽  
Chung‐Yeon Hwang ◽  
Tae‐Yong Shin ◽  
Hyung‐Min Kim

2003 ◽  
Vol 31 (5) ◽  
pp. 925-929 ◽  
Author(s):  
R.S. Lewis

[Ca2+]i (intracellular Ca2+ concentration) oscillations play a central role in the activation of T-lymphocytes by antigen. Oscillations in T-cells are absolutely dependent on Ca2+ influx through store-operated CRAC channels (Ca2+-release-activated Ca2+ channels), and evidence suggests that they arise from delayed interactions between these channels and Ca2+ stores. Their potential functions have been explored by creating controlled [Ca2+]i oscillations with pulses of Ca2+ entry or pulses of Ins(1,4,5)P3. Oscillations enhance both the efficiency and specificity of signalling through the Ca2+-dependent transcription factors nuclear factor of activated T-cells (NFAT), Oct/Oap and nuclear factor κB (NFκB) in ways that are consistent with each factor's Ca2+ dependence and kinetics of activation and deactivation. These studies show how [Ca2+]i oscillations may enhance signalling to the nucleus, and suggest a possible cellular mechanism for extracting information encoded in oscillation frequency.


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