Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New TNFR Signaling Mechanism Discovered

18.07.2008
A team of researchers at the University of California, San Diego School of Medicine has uncovered a new signaling mechanism used to activate protein kinases that are critical for the body’s inflammatory response. Their work will be published in the July 18 online edition of Science (Science Express).

“In addition to helping explain the basic mechanisms of transmembrane receptor signaling, these results may identify a potential therapy for interfering with inflammation,” said Michael Karin, Ph.D., professor of pharmacology and pathology in UC San Diego’s Laboratory of Gene Regulation and Signal Transduction.

The tumor necrosis factor (TNF) receptor (TNFR) family codes for a large number of cell surface receptors of great biomedical importance, and its signaling mechanisms have been the subject of intense investigation during the past decade. Specific inhibitors of TNF receptor 1 (TNFR1) activation are being used in the treatment of rheumatoid arthritis, psoriasis and inflammatory bowel disease, and receptor activator of NF-êB (RANK) inhibitors were recently found to be effective in the treatment of osteoporosis and other bone loss diseases.

Now Atsushi Matsuzawa, Ph.D., and Ping-Hui Tseng, Ph.D., postdoctoral fellows in the Karin laboratory, describe how engagement of CD40, a member of the TNFR family, results in assembly of multiprotein signaling complexes at the receptor. However, according to the researchers – and contrary to previous expectations – signaling cascades that lead to activation of Jun Kinases (JNK) and p38 MAP Kinases (MAPK) are not initiated until these complexes dissociate from the receptor.

... more about:
»TNFR »mechanism »receptor

The authors found that complex translocation from the cell surface receptor to the cytoplasm, which is required for JNK and p38 activation, depends on degradation of a signaling protein called TRAF3. This process can be inhibited by a class of compounds known as Smac mimics.

“As Smac mimic compounds do not interfere with the activation of NF-êB-dependent innate immunity but do prevent the induction of JNK- and p38- dependent inflammatory mediators, they may serve as the prototypes for new anti-inflammatory therapy,” said Karin, who also noted that current drugs that work by interfering with TNFR signaling exceed $5 billion a year in revenue.

Additional contributors include Sivakumar Vallabhapurapu, Jun-Li Luo and Weizhou Zhang, Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, UCSD School of Medicine; Haopeng Wang and Dario A. A. Vignali, Department of Immunology, St. Jude Children’s Research Hospital, Memphis; and Ewen Gallagher, Department of Immunology, Imperial College, London, Faculty of Medicine, Norfolk Place, London. Work was supported by grants from the National Institutes of Health, the Leukemia and Lymphoma Society, The Mochida Memorial Foundation for Medical and Pharmaceutical Research, American Lung Association of California and Life Science Foundation; a Cancer Center Support CORE grant and the American Lebanese Syrian Associated Charities (ALSAC). Karin is an American Cancer Society Research Professor.

Debra Kain | Newswise Science News
Further information:
http://www.ucsd.edu

Further reports about: TNFR mechanism receptor

More articles from Life Sciences:

nachricht Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology

nachricht The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>