Science Current Events | Science News | Brightsurf.com
 

Dynamics of crucial protein 'switch' revealed

May 18, 2011

Cell signaling networks tied to diabetes and cancer

Researchers at the University of Texas Medical Branch at Galveston and the University of California-San Diego School of Medicine have published a study that offers a new understanding of a protein critical to physiological processes involved in major diseases such as diabetes and cancer. This work could help scientists design drugs to battle these disorders.

The article was deemed a "Paper of the Week" by and will be on the cover of the Journal of Biological Chemistry. It is scheduled for publication May 20 and now available online.

"This study applied a powerful protein structural analysis approach to investigate how a chemical signal called cAMP turns on one of its protein switches, Epac2," said principal investigator Xiaodong Cheng, professor in the Department of Pharmacology and Toxicology and member of the Sealy Center for Structural Biology and Molecular Biophysics at UTMB.

The cAMP molecule controls many physiological processes, ranging from learning and memory in the brain and contractility and relaxation in the heart to insulin secretion in the pancreas. cAMP exerts its action in cells by binding to and switching on specific receptor proteins, which, when activated by cAMP, turn on additional signaling pathways.

Errors in cell signaling are responsible for diseases such as diabetes, cancer and heart failure. Understanding cAMP-mediated cell signaling, in which Epac2 is a major player, likely will facilitate the development of new therapeutic strategies specifically targeting the cAMP-Epac2 signaling components, according to the researchers.

The project involved an ongoing collaboration between Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr. and colleagues at UCSD, pioneers in the development and application of hydrogen/deuterium exchange mass spectrometry (DXMS) technology. Compared with other protein-analysis techniques, DXMS is especially good at studying the structural motion of proteins.

Using this novel approach, the investigators were able to reveal, in fine detail, that cAMP interacts with its two known binding sites on Epac2 in a sequential fashion and that binding of cAMP changes the shape of the protein in a very specific way - switching on its activity by exposing further signaling interaction sites on Epac2.

"DXMS analysis has proved to be an amazingly powerful approach, alone or in combination with other techniques, in figuring out how proteins work as molecular machines, changing their shapes - or morphing - in the normal course of their function," said Woods. "This will be of great use in the identification and development of therapeutic drugs that target these protein motions."

###

Collaborators include Tamara Tsalkova and Fang Mei of the UTMB Department of Pharmacology and Toxicology; Mark A. White, associate professor in the UTMB Department of Biochemistry and Molecular Biology; and Dr. Sheng Li, Dr. Tong Liu and Daphne Wang of the UCSD Department of Medicine and Biomedical Sciences Graduate Program.

The study was funded by the National Institutes of Health and the John Sealy Memorial Endowment Fund for Biomedical Research. Based on its success at applying DXMS to the analysis of a number of important proteins, exemplified by this study with UTMB researchers, UCSD recently was awarded a generous NIH grant to implement "next-generation" advanced DXMS analysis for the benefit of scientists throughout the United States.

University of Texas Medical Branch at Galveston


Related Chemical Signal Current Events and Chemical Signal News Articles


Slime mold reveals clues to immune cells' directional abilities
How white blood cells in our immune systems home in on and engulf bacterial invaders--like humans following the scent of oven-fresh pizza--has long been a mystery to scientists.

Targeted orphaned domain may lead to drug therapies
"Pentameric quaternary structure of the intracellular domain of serotonin type 3A receptors," was published in the April issue of Scientific Reports. Along with her research team, Akash Pandhare, Ph.D., and Petar N. Grozdanov, Ph.D., Jansen's research demonstrated for the first time that the serotonin type 3A (5-HT3A) ICD assembles into stable pentamers in solution in the absence of the other two domains, thought to be the drivers for oligomerization.

New fluorescent probes help solve cell membrane mystery
Scientists from Japan, India and the U.S. have observed raft domains -- active sections of the cell membrane with special groups of molecules -- in live cells for the first time. Their findings will be published this week in Nature Chemical Biology.

Scientists find brain plasticity assorted into functional networks
The brain still has a lot to learn about itself. Scientists at the Virginia Tech Carilion Research Institute have made a key finding of the striking differences in how the brain's cells can change through experience.

Study offers insight on how a new class of antidepressants works
A new class of drugs under development to treat depression has shown some success by targeting brain cells' ability to respond to the chemical messenger glutamate. But the mechanism by which these experimental therapies work has remained unknown.

Individuals with social phobia have too much serotonin -- not too little
Previous studies have led researchers to believe that individuals with social anxiety disorder/ social phobia have too low levels of the neurotransmitter serotonin.

Researchers discover new ways to shut down signals involved in brain diseases
A research team based at the University of Eastern Finland and the Turku Centre for Biotechnology have found new ways to block a pathway that may be responsible for several brain disorders, which could open the door to developing better treatments.

Dying cells can protect their stem cells from destruction
Cells dying as the result of radiation exposure or chemotherapy can send a warning to nearby stem cells. The chemical signal allows the stem cells to escape the same fate, University of Washington researchers report in the May 11 issue of the journal Nature Communications.

New strategy to protect healthy gut microbes from antibiotics
Gut microbes promote human health by fighting off pathogens, but they also contribute to diseases such as diabetes and cancer.

Cells can use dynamic patterns to pluck signals from noise
Scientists have discovered a general principle for how cells could accurately transmit chemical signals despite high levels of noise in the system, they report in Science this week.
More Chemical Signal Current Events and Chemical Signal News Articles

US Army Order of Battle, 1919-1941: Volume 4 - The Services: Quartermaster, Medical, Military Police, Signal Corps, Chemical Warfare, and Miscellaneous Organizations, 1919-41 (Part 1)

US Army Order of Battle, 1919-1941: Volume 4 - The Services: Quartermaster, Medical, Military Police, Signal Corps, Chemical Warfare, and Miscellaneous Organizations, 1919-41 (Part 1)
by Lieutenant Colonel (Retired) Steven E. Clay (Author)


Steve Clay’s massive work, “US Army Order of Battle, 1919–1941,” is, in many respects, the story of the American Army, its units, and its soldiers, during a period of neglect by a parsimonious Congress and others who perhaps believed in the notion that a “War to End All Wars” had actually been fought. Indirectly, it tells the story of a diminutive Regular Army that continued to watch faithfully over the ramparts of freedom in far-flung outposts like Panama, Alaska, the Philippines, and China, as well as the many small and isolated garrisons throughout the United States; a National Guard that was called on frequently by various governors to prevent labor troubles, fight forest fires, and provide disaster relief to their state’s citizens; and an Organized Reserve whose members...

US Army Order of Battle, 1919-1941: Volume 4 - The Services: Quartermaster, Medical, Military Police, Signal Corps, Chemical Warfare, and Miscellaneous Organizations, 1919-41 (Part 2)

US Army Order of Battle, 1919-1941: Volume 4 - The Services: Quartermaster, Medical, Military Police, Signal Corps, Chemical Warfare, and Miscellaneous Organizations, 1919-41 (Part 2)
by Lieutenant Colonel (Retired) Steven E. Clay (Author)


Steve Clay’s massive work, “US Army Order of Battle, 1919–1941,” is, in many respects, the story of the American Army, its units, and its soldiers, during a period of neglect by a parsimonious Congress and others who perhaps believed in the notion that a “War to End All Wars” had actually been fought. Indirectly, it tells the story of a diminutive Regular Army that continued to watch faithfully over the ramparts of freedom in far-flung outposts like Panama, Alaska, the Philippines, and China, as well as the many small and isolated garrisons throughout the United States; a National Guard that was called on frequently by various governors to prevent labor troubles, fight forest fires, and provide disaster relief to their state’s citizens; and an Organized Reserve whose members...

Chemical Signals in Vertebrates 13

Chemical Signals in Vertebrates 13
by Bruce A. Schulte (Editor), Thomas E. Goodwin (Editor), Michael H. Ferkin (Editor)


In 2014, the Chemical Signals in Vertebrates (CSiV) group held its 13th triennial meeting in conjunction with the 30th meeting of the International Society of Chemical Ecology (ISCE). The meeting convened on the campus of the University of Illinois at Urbana-Champaign. This meeting was the first held jointly with these two groups, which share common history and are dedicated to understanding the role of chemical communication in the lives of organisms. This volume is a collection of the proceedings of this meeting and, like the meeting, cover a variety of topics in chemical ecology, including Chemical Ecology of Social Behavior; Chemical Signals – Analysis and Synthesis; Evolution, Genomics, and Transcriptomics of Chemical Signals; Molecular Mechanisms of Semiochemical...

U.S. Army Commander's Battle Staff Handbook with Garrison Duties - Fire Support Officer, Engineer, Air Defense Artillery, Signal, Chemical, Chaplain - Determining Staff Functional Capability

U.S. Army Commander's Battle Staff Handbook with Garrison Duties - Fire Support Officer, Engineer, Air Defense Artillery, Signal, Chemical, Chaplain - Determining Staff Functional Capability
by U.S. Government (Author), Department of Defense (Author), U.S. Army (Author)


This Research Product, prepared for the Deputy Commanding General for Training, U.S. Army Combined Arms Command, Fort Leavenworth, Kansas, presents information for the maneuver battalion commander and staff to consider. It provides information to determine staff functional capability, assess staff actions, and provide fundamental references for inexperienced staff officers. It describes the core duties of battalion staff officers and key slice liaison officers on the battle staff. Feedback from field commanders, combat training center (CTC) observations, and research conducted by the Training Systems Research Division of the U.S. Army Research Institute for the Behavioral and Social Sciences supports the need for staff training at the battalion level. The results of this effort have...

Chemical Signals in Vertebrates 6 (v. 6)

Chemical Signals in Vertebrates 6 (v. 6)
by R.L. Doty (Editor), Dietland Müller-Schwarze (Editor)


This volume is an up-to-date treatise of chemosensory vertebrate research performed by over 200 scientists from 22 countries. Importantly, data from over 25 taxa of vertebrates are presented, including those from human beings. Unlike other volumes on this topic, a significant nurober of the contributions come from leading workers in the former Soviet Union and reflect studies within a wide variety of disciplines, including behavior, biochemistry, ecology, endocrinology, genetics, psychophysics, and morphol­ ogy. Most of the studies described in this volume were presented at the Chemical Signals in Vertbrates VI (CSV VI) symposium held at the University of Pennsylvania in the summer of 1991. This international symposium was the largest and the most recent of a series of six such symposia,...

Pheromones and Animal Behavior: Chemical Signals and Signatures

Pheromones and Animal Behavior: Chemical Signals and Signatures
by Tristram D. Wyatt (Author)


Pheromones and other kinds of chemical communication underlie the behavior of all animals. Building on the strengths of the first edition, widely recognized as the leading text in the subject, this is a comprehensive overview of how pheromones work. Extensively revised and expanded to cover advances made over the last ten years, the book offers a thorough exploration of the evolutionary and behavioral contexts of chemical communication along with a detailed introduction to the molecular and neural basis of signal perception through olfaction. At a time of ever increasing specialization, Wyatt offers a unique synthesis, integrating examples across the animal kingdom. A final chapter critically considers human pheromones and the importance of olfaction to human biology. Its breadth of...

Signal Transduction by Reactive Oxygen and Nitrogen Species: Pathways and Chemical Principles

Signal Transduction by Reactive Oxygen and Nitrogen Species: Pathways and Chemical Principles
by H.J. Forman (Editor), J.M. Fukuto (Editor), M. Torres (Editor)


Henry Jay Forman, Jon Fukuto and Martine Torres "Research is to see what everybody else has seen and to think what nobody else has thought. " -- Albert Szent-Gyorgyi Several years ago, one of us put together a book that dealt with various aspects of oxidative stress and introduced the concept of signal transduction by oxidants. Since then, the interest in the mechanisms by which reactive oxygen and nitrogen species (ROS/RNS) can modulate the cell’s response has tremendously grown, paralleling the intense efforts towards identifying new signaling pathways in which phosphorylation/dephosphorylation events take center stage. Evidence is now mounting that production of these species by the cells is required for their function from growth to apoptosis and numerous signaling pathways have...

Bombardier Beetles And Fever Trees: A Close-up Look At Chemical Warfare And Signals In Animals And Plants (Helix Books)

Bombardier Beetles And Fever Trees: A Close-up Look At Chemical Warfare And Signals In Animals And Plants (Helix Books)
by William Agosta (Author)


In their sometimes fierce, often mysterious lives, many plants and animals rely on the transmission and reception of chemicals to attack, defend, eat, and avoid being eaten. In this exciting book, Agosta tells the story of the surprising interplay between the hunters and the hunted in the gardens, fields, and forests of the world.

The Services: Quartermaster, Medical, Military Police, Signal Corps, Chemical Warfare, and Miscellaneous Organizations, 1919–41 (US Army Order of Battle 1919–1941)

The Services: Quartermaster, Medical, Military Police, Signal Corps, Chemical Warfare, and Miscellaneous Organizations, 1919–41 (US Army Order of Battle 1919–1941)


The purposes of US Army Order of Battle 1919–1941 are threefold. The first is to fill a void in the published record of US Army units documented by Order of Battle of the United States Land Forces in the World War published by the Center of Military History and Mr. Shelby L. Stanton’s Order of Battle,
U.S. Army World War II. The second is to provide Army command historians, unit historians, and other individuals who are trying to research specific unit histories a basic overview of what these units were doing in the interwar period, where the units were located, and who commanded them. The third is to provide a private individual who had a relative who served during this period, and who wishes to know what that service may have consisted of, an account of the major activities in...

The Hidden Power of Smell: How Chemicals Influence Our Lives and Behavior

The Hidden Power of Smell: How Chemicals Influence Our Lives and Behavior
by Paul A. Moore (Author)


The main purpose of the book is to provide insight into an area that humans often take for granted. There are wonderful and exciting stories of organisms using chemical signals as a basis of a sophisticated communication system. In many instances, chemical signals can provide more detailed and accurate information than any other mode of communication, yet this world is hidden from us because of our focus on visual and auditory signals.​ Although we have a diversity of senses available to us, humans are primarily auditory and visual animals. These stimuli are sent to the more cognitive areas of our brain where they are immediately processed for information. We use sounds to communicate and music to excite or soothe us. Our vision provides us with communication, entertainment, and...

© 2017 BrightSurf.com