Navigation Links
How the tilt of a cell-surface receptor prevents cancer
Date:1/31/2013

y subsequently showed that a mutation of one of those amino acidsknown as tryptophan, and symbolized by the letter Wfound at position 515, led to the receptor's permanent activation in mice. Constantinescu and his colleagues predicted then that mutations of W515 would turn up in human cancersand were proved correct by other laboratories and their own studies. "But what remained unclear for the field," says Constantinescu, "was why this tryptophan in particular is so important, why, if you mutate it, TpoR is spontaneously activated."

Biochemical and functional analyses of mutant and normal TpoR conducted by Constantinescu's lab and structural studies of receptors conducted by Smith's lab, established that the tryptophan has a pronounced effect on the function of TpoR through control of the receptor's spatial orientation. "Basically, we found that the tryptophan forces TpoR to tilt," says Constantinescu. "This means that when two normal TpoRs that have not yet been switched on by thrombopoietin come together in the cellular membrane, the tilted coils that normally span the membrane cross each other to form something like an X, not two parallel lines. When parallel, these coils attract each other specifically. Tilting prevents the two coils from contacting each other within the membrane and, in effect, prevents their spontaneous activation."

"If you replace the tryptophan with a variety of amino acids other than tryptophan," explains Constantinescu, "the receptor straightens up. It can then pair up with another TpoReven without thrombopoietin bindingand begin signaling continuously." The result, it would appear, is the unrestrained transmission of proliferative signals and the development of ET and primary myelofibrosis.

This finding is significant for both the basic science of signal transduction and applied cancer research. Tryptophan is found at similar points in some other cell surface receptors, but molecular biologists had presumed tha
'/>"/>

Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

Page: 1 2 3

Related biology news :

1. Measuring progesterone receptor expression to improve hormone-receptor-positive cancer management
2. G protein-coupled receptor mediates the action of castor oil
3. BUSM study identifies receptors role in regulating obesity, type 2 diabetes
4. Cell receptor has proclivity for T helper 9 cells, airway inflammation
5. Steroid hormone receptor prefers working alone to shut off immune system genes
6. Jackson Laboratory researchers provide definitive proof for receptors role in synapse development
7. Dopamine-receptor gene variant linked to human longevity
8. Stay-at-home transcription factor prevents neurodegeneration
9. Inhibition of enzyme NOX4 prevents liver fibrosis
10. Tortoise and the hare: New drug stops rushing cancer cells, slow and steady healthy cells unharmed
11. Embryonic development protein active in cancer growth
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2015)... 2015 The biologics safety testing market is ... the market include growth of the pharmaceutical and biological ... Over the years, the number of drug approvals in ... the FDA approved 225 drug applications and Health Canada ... Europe accounted for 3,822 of the pharmaceutical ...
(Date:6/24/2015)... , June 24, 2015 Biometry authentication ... emerging biometric password solution one face in. ... one face in, entering the expanding ... and affordable multifactor-authentication biometric answer to the password ... provided in partnership with KeyLemon, one face in ...
(Date:6/23/2015)... PALM BEACH GARDENS, Fla. , June ... of multi-factor identity management and authentication solutions, today ... Altus strong, multi-factor authentication solution.  The ... ease of use of the DigitalPersona Altus ... and biometric reader compatibility. In ...
Breaking Biology News(10 mins):Biological Safety Testing Market by Application, Product, & Test - Global Forecast to 2019 2Biological Safety Testing Market by Application, Product, & Test - Global Forecast to 2019 3Biological Safety Testing Market by Application, Product, & Test - Global Forecast to 2019 4KeyLemon Announces Partnership With Biometric Password Solution onefacein 2Crossmatch Releases Enhanced DigitalPersona Altus Advanced Authentication Functionality 2
... out of the University of Alberta for those who may have ... medical researchers have found a way to reduce the amount of ... from food the body metabolizes, a key discovery that could lead ... 2 diabetes and heart disease related to obesity. In ...
... A Web site is a better source of information ... to a study of low-income mothers reported in the January ... http://www.jneb.org/) . Led by Kami J. Silk, Ph.D., of ... mothers with nutrition information in different formats. One group ...
... cause of sudden cardiac death even when it isnt overdosed ... chronic pain or drug addiction withdrawal, a new study by ... findings, described in the January 2008 issue of The American ... sudden cardiac deaths in the greater Portland, Ore., metropolitan area ...
Cached Biology News:University of Alberta researchers report breakthrough in lowering bad cholesterol, fatty acid levels 2For nutrition info, moms like the Web best 2Methadone even at therapeutic levels can kill 2Methadone even at therapeutic levels can kill 3
(Date:7/3/2015)... 2015 Forskare kan ... på  http://www.openinnovationinscience.at till det återkommande utbildningsprogrammet ... hålls i Wien .  ... internationella forskare och vetenskapsmän som genomfördes av ... största utmaningar bristen på incitament för att ...
(Date:7/2/2015)... Ill. , July 2, 2015 College ... Colton Eakins are gaining invaluable real-world experiences while ... Technology this summer. The students will be ... Jeff Wereszczynski,s research group at IIT. The internship ... Tom Carter , Physics; Dr. Kathy Finan ...
(Date:7/1/2015)... ... July 01, 2015 , ... It is now possible to separate ... single photon emission computed tomography (SPECT) according to researchers from Amen Clinics, UCLA, ... 20,000 brain scans and is believed to be the largest brain imaging study ever, ...
(Date:7/1/2015)... , July 1, 2015   Neuraltus Pharmaceuticals, ... development of groundbreaking drugs to treat neurodegenerative diseases ... that Robert G. Miller , M.D., Director of ... Health,s California Pacific Medical Center in San Francisco, has ... for $1.5 million to help fund a Phase ...
Breaking Biology Technology:Lansering av världens första program för öppen innovation för att utbilda forskare 2Lansering av världens första program för öppen innovation för att utbilda forskare 3COD Students Participate in Prestigious Summer Internships 2Brain Scans Can Tell Post-Traumatic Stress Disorder and Traumatic Brain Injury Apart According to New Research by Amen Clinics 2Brain Scans Can Tell Post-Traumatic Stress Disorder and Traumatic Brain Injury Apart According to New Research by Amen Clinics 3Brain Scans Can Tell Post-Traumatic Stress Disorder and Traumatic Brain Injury Apart According to New Research by Amen Clinics 4Investigator to Receive $1.5 Million Grant from the ALS Association to Help Fund Confirmatory Phase 2 Study of Neuraltus Pharmaceuticals' NP001 2Investigator to Receive $1.5 Million Grant from the ALS Association to Help Fund Confirmatory Phase 2 Study of Neuraltus Pharmaceuticals' NP001 3Investigator to Receive $1.5 Million Grant from the ALS Association to Help Fund Confirmatory Phase 2 Study of Neuraltus Pharmaceuticals' NP001 4
... Inc. announced that the launch of a new ... of cancer treatments.  BioSpeciFx® is composed of carefully ... biomarker tests that identify critical molecular targets within ... by BioSpeciFx® in combination with Precision,s sophisticated drug ...
... Texas, April 7, 2011 Wound Management Technologies, Inc., ... leader in advanced wound care solutions, today announced that ... care products within key international markets, has received new ... gel products.  In Lebanon, the subsidiary just completed a ...
... Reportlinker.com announces that a new market research report ... Industrial Biotechnology China News 1103 ... government was reported to continue intensifying the demand ... (2011-2015) Plan. This act is expected to help ...
Cached Biology Technology:Precision Therapeutics Announces New Tumor Profiling Product to Augment Utility of ChemoFx® and Further Personalize Cancer Treatment 2WNDM Secures Additional International Sales; $150 K in New Orders for 2011 2WNDM Secures Additional International Sales; $150 K in New Orders for 2011 3Reportlinker Adds Industrial Biotechnology China News 1103 2Reportlinker Adds Industrial Biotechnology China News 1103 3