Navigation Links
Discovery of 'overdrive' protein could broaden drug design options
Date:2/12/2008

CHAPEL HILL New research by scientists at the University of North Carolina at Chapel Hill shows for the first time that an important family of proteins known to function at the cell surface also functions at a site within the cell.

The findings have potential implications for drug development as they involve G protein-coupled receptors (GPCRs). These molecules are the target of forty to fifty percent of modern medicinal drugs, such as antihistamines and drugs for high blood pressure.

The study identified the first protein to activate the G-protein signaling pathway from within a cell. In humans, reactions to everything from taste and smell to stimulants like adrenaline or caffeine requires G-protein signaling.

Until now, the only known way to turn on a G-protein was via a receptor sitting on a cells surface membrane. This receptor acts like a telegraph operator, accepting outside signals and relaying them inside the cell. It converts an external signal, like caffeine, into action in this case, a nerve signal to the brain.

More than half of all drugs, from asthma and heart medicine to antidepressants, target G-protein receptors. Discovering a protein that activates G-proteins from inside a cell could open up an entirely new pathway for drug development, said Henrik Dohlman, Ph.D., senior study author and a professor of biochemistry and biophysics in UNCs School of Medicine.

No drug is 100 percent effective, 100 percent free of side effects and 100 percent safe. The more options we have biochemically, the more selective we can be in designing new drugs. If we can find another way of modulating G-proteins, we could expand the drug targets that are available to pharmacology, Dohlman said.

The study appeared online Feb.7, 2008, in the journal Current Biology and will be published in the Feb. 14, 2008, print edition. Funding was provided by the National Institutes of Health and a UNC Cell and Molecular Biology Program predoctoral fellowship.

Despite 20 years of study, G-protein signaling continues to produce surprises. The advent of the human genome project revealed that some three percent of our DNA is dedicated to these messenger molecules. However, the genomic data also drew biologists away from the research technique the UNC team used to discover the new protein, Dohlman said. People stopped looking for things that could activate G-proteins using functional criteria, he said. Instead, they searched for new receptors and activators based on common genetic patterns.

Mike Lee, a graduate student in the UNC School of Medicines department of pharmacology, identified the new protein, called Arr4, in yeast cells. Lee employed a mutant form of G-protein to search for any messengers inside the yeast cell with an affinity for G-proteins.

We went looking for things that could activate G-proteins but dont resemble known receptors, Lee said.

He identified seven proteins that werent receptors, but did bind to G-proteins, and did further tests on one of the seven proteins, Arr4, to determine its function.

In yeast, Arr4 is involved in cell fusion, a process in which two yeasts fuse together to form one cell, combining their genetic data. A G-protein coupled receptor (GPCR) controls cell fusion, while Arr4 appears to play a supporting role.

Lee said he thinks that Arr4 may allow the cell to go through several additional rounds of signal activation without needing to go back to the receptor.

Our current thinking is its not so much that this is the ignition for signaling, its more like an overdrive. Once the pathway is activated by the hormone outside, Arr4 sustains the activity inside, Lee said. What we dont know is if Arr4 is itself simulated by some signal, and of course were very interested in finding out if thats the case.


'/>"/>

Contact: Leslie Lang
llang@med.unc.edu
919-843-9687
University of North Carolina at Chapel Hill
Source:Eurekalert

Related medicine news :

1. Discovery of sugar sensor in intestine could benefit diabetes
2. Discovery suggests location of genes for breast density, a strong risk factor for breast cancer
3. Stem cell research produces a key discovery for Fragile X Syndrome
4. Welch Foundation gives $1.6 million for drug discovery research
5. New discovery leaves blood-doping athletes scratching their heads
6. Chemical Diversity Initiates International Prostrate Cancer Discovery Partnership
7. New discovery leaves blood-doping athletes scratching their heads
8. Discovery of widespread tumor growth gene holds promise for effective anti-cancer treatment
9. Discovery supports theory of Alzheimers disease as form of diabetes
10. Discovery Health CME Explores the Benefits and Risks of Aspirin in Aspirin Therapy: Maximizing the Benefits
11. New discovery may improve treatment of one of the worlds leading causes of blindness
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/19/2017)... Rochester, NY (PRWEB) , ... January 19, 2017 ... ... release of Clinical Conductor CTMS, which provides a modern CTMS workflow designed to ... patient management information has been condensed to a single page, maximizing usability and ...
(Date:1/19/2017)... , ... January 19, 2017 , ... ... and staff members in 2017 who are passionate about making a difference in ... 1994 and headquartered in Tampa, UMA, a nonprofit healthcare educational institution, has more ...
(Date:1/19/2017)... NJ (PRWEB) , ... January 19, 2017 , ... ... locally owned insurance agency which serves Lawrenceville, New Jersey and the surrounding area, ... , Amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig's disease ...
(Date:1/19/2017)... ... January 18, 2017 , ... The CHP suggests that California drivers can avoid ... slowing down and increasing the space between themselves and other vehicles, according to a ... attorney Raymond R. Hassanlou notes that, rain or shine, drivers should always incorporate safe ...
(Date:1/19/2017)... ... January 19, 2017 , ... "ProParagraph Basics is a set ... process for all media productions," said Christina Austin - CEO of Pixel Film ... self-animating paragraphs designed for multi-lined text purposes. Choose from presets with basic, ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... 19, 2017 The global  pacemaker market  is expected to ... View Research, Inc. The heightening prevalence of cardiac conditions coupled with the availability ... globally. In addition, technological enhancements in these devices are supporting the expansion of ... ... Grand View Research Logo ...
(Date:1/19/2017)... , Jan. 18, 2017  ViewRay, Inc. ... world,s first and only clinical MRI-guided radiation therapy ... proceeds of approximately $26.1 million through a private ... Capital Management led the financing and was joined ... Advisors, LLC and Kearny Venture Partners, and an ...
(Date:1/19/2017)... 2017  Magnetic Insight Inc., leader in magnetic ... agreement with inviCRO LLC to develop intuitive image ... based on inviCRO,s VivoQuantâ„¢ visualization and post processing ... complete MPI solution package with the Momentum MPI ... imaging in vivo. MPI is a ...
Breaking Medicine Technology: