Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inflammation 'on switch' also serves as 'off switch'

22.01.2010
In a surprising finding, researchers at North Carolina State University have discovered the critical importance of a protein previously believed to be a redundant “on switch” for certain immune-system responses.

Scientists previously understood that the protein called TAB2 activates inflammation, an important biological process that stimulates wound-healing and prevents invasion of harmful organisms. But scientists considered TAB2 nonessential to the process due to the redundant function of a cousin protein, called TAB3, which has no trouble serving as an “on switch” to activate the inflammation process in TAB2’s absence.

In a study published in the Jan. 22 edition of the Journal of Biological Chemistry, the NC State researchers show that underestimating TAB2 can be dangerous. Rather than merely serving as an “on switch,” TAB2 also serves as an “off switch” that turns off the inflammation process. When TAB2 is absent or knocked out in cell cultures, the inflammation process continues unabated.

Too much inflammation can be a really bad thing. It is associated with human diseases including certain cancers, inflammatory bowel syndrome and psoriasis.

Knowing more about the regulatory mechanisms in cells may one day lead to drugs that can target excessive inflammation, say NC State’s Dr. Jun Ninomiya-Tsuji, associate professor of environmental and molecular toxicology, and her graduate student, Peter Broglie, the lead authors of the paper describing the study.

In the study, Ninomiya-Tsuji and Broglie show that cells lacking TAB2 had a prolonged inflammation response. Normally, TAB2 can be counted on to bring a protein called TAK1 close to tumor necrosis factor, or TNF, a circulating molecule that is a normal component of the immune system. Bringing TAK1 close to TNF activates TAK1, thereby starting the inflammatory response.

In normal systems, this inflammatory response would be quickly regulated to prevent too much inflammation. This is done by a regulating molecule called PP6, which deactivates TAK1, and, therefore, the inflammation process. When TAB2 was absent or knocked out, however, PP6 did not shut down TAK1. The NC State scientists infer, then, that TAB2 has a heretofore unknown function – it brings TAK1 close enough to PP6 to halt the inflammation process.

The NC State scientists were so surprised by the finding that, Broglie says, “Dr. Ninomiya-Tsuji made me replicate the study three times.”

The study was funded by a grant to Ninomiya-Tsuji from the National Institutes of Health. Co-authors of the paper included scientists from the University of Virginia and two Japanese universities – Nagoya University and Osaka University.

- kulikowski -

Note: An abstract of the paper follows.

“A TAK1 kinase adaptor, TAB2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in TNF signaling pathway”

Authors: Peter Broglie and Jun Ninomiya-Tsuji, North Carolina State University; Kunihiro Matsumoto, Nagoya University; Shizuo Akira, Osaka University; David L. Brautigan, University of Virginia

Published: Jan. 22, 2010, in Journal of Biological Chemistry

Abstract: TAK1 kinase is an indispensable signaling intermediate in TNF, IL-1, and Toll-like receptor signaling pathways. TAK1 binding protein 2 (TAB2) and its closely related protein, TAB3, are binding partners of TAK1, and have previously been identified as adaptors of TAK1 that recruit TAK1 to a TNF receptor signaling complex. TAB2 and TAB3 redundantly mediate activation of TAK1. In this study, we investigated the role of TAB2 by analyzing fibroblasts having targeted deletion of tab2 gene. In TAB2-deficient fibroblasts, TAK1 was associated with TAB3 and activated following TNF stimulation. However, TAB2-deficient fibroblasts displayed a significantly prolonged activation of TAK1 compared with wild type control cells. This suggests that TAB2 mediates deactivation of TAK1. We found that a TAK1 negative regulator, protein phosphatase 6 (PP6), was recruited to TAK1 complex in wild type but not in TAB2-deficient fibroblasts. Furthermore, we demonstrated that both PP6 and TAB2 interacted with the polyubiquitin chains and this interaction mediated the assembly with TAK1. Our results indicate that TAB2 not only activates TAK1 but also plays an essential role in the deactivation of TAK1 by recruiting PP6 through a polyubiquitin chain-dependent mechanism.

Mick Kulikowski | EurekAlert!
Further information:
http://www.ncsu.edu

More articles from Life Sciences:

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

nachricht Snap, Digest, Respire
20.01.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Bodyguards in the gut have a chemical weapon

20.01.2017 | Life Sciences

SF State astronomer searches for signs of life on Wolf 1061 exoplanet

20.01.2017 | Physics and Astronomy

Treated carbon pulls radioactive elements from water

20.01.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>