Does HBV infection induce acute cellular DNA damage?
... immunofluorescence to show ATR foci ands Chk1 phosphorylation
foci formation; flow cytometry to analyze the ... steady state of ATR protein and increased phosphorylation
of multiple downstream targets including Chk1, ... ATM at Ser-1981 and its downstream substrate Chk2 phosphorylation
at Thr-68 did not visibly increase upon ....
Lifestyle can alter gene activity, lead to insulin resistance
... expression of genes of mitochondrial oxidative phosphorylation
in monozygotic twins discordant for obesity," ... to the defects in mitochondrial oxidative phosphorylation
described in type 2 diabetic patients and ... levels of genes encoding mitochondrial oxidative phosphorylation
in obesity is influenced by environmental and ...
Major 'missed' biochemical pathway emerges as important in virtually all cells
... system is analogous to the much more studied phosphorylation
system, in which phosphates are added and removed from proteins, the paper said. Changes in phosphorylation
are among the most common causes of disease, and proteins that regulate phosphorylation
are major drug targets, Stamler said.
New research provides dynamic visualization of simplest circadian clock
Considerable research has implicated the phosphorylation
cycle of KaiC as the central pacemaker in ... assembly/disassembly dynamics and the circadian phosphorylation
of KaiC is still poorly understood, mainly ... stage but are passively driven by the phosphorylation
status of KaiC in the late oscillatory stage. ...
Atypical protein kinase C stabilizes SRC-3 levels in breast cancer cells
... including SRC-3.
Recently, it was shown that phosphorylation
of SRC-3 by specific kinases is associated with ... cellular SRC-3 protein levels by inducing phosphorylation
of a particular region of SRC-3. Specifically, phosphorylation
of C-terminal residues induced a conformational ...
Pharmasset Nominates PSI-938 as a New Nucleotide Analog Inhibitor of Hepatitis C for Preclinical Development
... a complementary resistance profile and is metabolized through a different phosphorylation
pathway," stated Michael Otto, PhD, Pharmasset's Chief Scientific Officer. ... and are metabolized to the active triphosphate form through a different phosphorylation
pathway than the pyrimidines. Given these characteristics, purine and ...
Stanford researchers harness nanoparticles to track cancer-cell changes
... one common way for proteins to get activated is through a process called phosphorylation
that slightly changes a protein's shape, in effect turning it on.
Two ... of cancer. The Stanford team was able to simultaneously monitor changes in phosphorylation
levels of both proteins in lab-cultured myeloid leukemia cells. The ...
New alternative to biopsy detects subtle changes in cancer cells, Stanford study shows
... from others.
Finally, they were able to detect subtle differences in phosphorylation
in several other cancer-associated proteins. "Some of these proteins can ... research in the Felsher lab, the lipid-lowering drug atorvastatin reduces phosphorylation
of yet another cancer-associated protein. "This is the first time we've ...
E. coli persists against antibiotics through HipA-induced dormancy
... professor of biochemistry and molecular biology. While other types of phosphorylation
occur in bacteria, HipA phosphorylates proteins at their serine or ... to adenosine triphosphate (ATP), a common characteristic of kinases. phosphorylation
occurs when an enzyme binds to both ATP and to its target protein.
Tailored Drug Delivery Reduces Adverse Effects After PCI
... stents at one month as measured by platelet reactivity
monitoring by VASP phosphorylation
analysis, a blood test that measures a
patient's anti-platelet response to ... hours with a goal of reducing their score to the cut-off level on
a VASP phosphorylation
analysis, a blood test that measures a patient's
anti-platelet response to ...
Scripps Florida scientists develop a process to disrupt hepatitis C virion production
... analyses, the authors were able to show that their deletion altered a phosphorylation
signal controlling the switch from RNA replication to virus particle ... University, comments, This is a spectacular advance linking a specific phosphorylation
event by a cellular kinase to hepatitis C virus assembly. Remarkably, the ...
Out-of-whack protein may boost Parkinson's
... vital for movement.
We know of several enzymes that can cause phosphorylation
in the proper position of the alpha-synuclein protein, said Oleg ... purposes.
Of the types of alpha-synuclein, the one that simulated phosphorylation
at position 129 of the protein was nontoxic. But the other versions of the ...
High zinc status in lung cells slows growth and induces DNA damage-induced gene expression
... indicated that the blockage was Gadd45 dependent. Moreover, the enhanced phosphorylation
of p38 and p53 (ser15) observed in ZS cells was normalized after suppression of Gadd45 by siRNA, implicating that the enhanced phosphorylation
of these proteins was Gadd45 dependent. Thus, the researchers demonstrated ...
Emory researchers identify signaling protein for multiple myeloma
... to turn-on RSK2 by FGFR3. FGFR3 impacts downstream proteins through phosphorylation
at special tyrosine sites.
We found that FGFR3 directly phosphorylates ... phosphorylated sequences and observe the global state of protein tyrosine phosphorylation
in cells and tissues.
Using this technology, says Dr. Chen, we ...
Protein-Folding Problem May Help Spur Alzheimer's
... at an early stage of neurofibrillary degeneration and ... that the prolonged activation of the [unfolded protein response] is involved in both tau phosphorylation
and neurodegeneration in [Alzheimer's disease] pathogenesis ... Future studies will address the therapeutic opportunities of this pathway for the ...
Scientists uncover secrets of potential bioterror virus
... Rift Valley fever virus from using cellular protein synthesis machinery to make the proteins it needs to replicate itself. But since NSs prevents the phosphorylation
of eIF2-alpha by taking out PKR, the virus is free to copy itself within host cells without interference.
"It's amazing that the virus evolved to ...
Oncogene inhibits tumor suppressor to promote cancer: Study links B-RAF and LKB1
... activated AMPK.
The researchers went on to show that LKB1 was phosphorylated by two kinases that are downstream of B-RAF, ERK and Rsk. The phosphorylation
of LKB1 interfered with the ability of LKB1 to bind and activate AMPK. Importantly, expression of mutant LKB1 that could not be phosphorylated ...
A potential approach to treatment of hepatitis B virus infection
... frequent viral polymerase mutations. We found that HBV infection triggered an ATR-dependent DNA damage response, resulting in increased ATR and Chk1 phosphorylation
levels, however, ATR checkpoint signaling was blocked downstream of the p53-dependent pathway to evade apoptosis by p21 degradation. We have designed ...
JCI online early table of contents: June 12, 2008
... now investigating ways in which this information can be used to develop new therapeutics for skeletal disorders that result in dwarfism.
of GSK-3-beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes
Plant flavonoid found to reduce inflammatory response in the brain
... (AP-1) from binding the IL-6 promoter.
AP-1 is in turn activated by JNK, an upstream protein kinase. Jang found that luteolin inhibited JNK phosphorylation
in microglial cell culture. The failure of the JNK to activate the AP-1 transcription factor prevented it from binding to the promoter region on the ...
Unexpected role: EGFR protects cancer cells from starving
... of cell membranes, where epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-a) can bind to the receptor, launching a molecular phosphorylation
cascade, which stimulates the cell to divide. This normal tyrosine kinase activity is put on overdrive in cancer cells because EGFR is heavily ...
Monoclonal antibody Hb3: A marker for colon cancer progression or as a therapeutic target?
... protein is 62.02 kDa, including one hydrophobic region, one transmembrane domain, five coiled coils, four glycosylation sites and forty-nine phosphorylation
sites. CKAP4-similar protein has high homogeneity with Np63, and the characteristic expression of agrNp63 alpha that is considered a potential ...
Mitochondria play role in pathogenesis of AD and estrogen-induced neuroprotection
... Presentation Award. He also received an AAA travel award.
Mitochondria, small organelles within the cells, use a process called Oxidative phosphorylation
to generate the vast majority of the adenosine triposphate (ATP) molecules that cells utilize to function properly. If the mitochondria become less ...
Lithium chloride slows onset of skeletal muscle disorder
... might translate to humans with IBM. They performed tests on human muscle tissue samples and found the GSK-3 beta enzyme again played a role in the phosphorylation
of tau. That was not the case, though, in patients with other muscle disorders. "This suggests that our IBM mouse model may have the same skeletal ...
Study: Brain connections strengthen during waking hours, weaken during sleep
... experiment, the scientists examined how many of the receptors underwent phosphorylation, another indicator of synaptic potentiation. They found phosphorylation
levels were much higher during waking than sleeping. The results were the same when they measured other enzymes that are typically active during ...
JCI online early table of contents: Jan. 2, 2008
... as a key step in the development of the disorder.
In the study, posttranslational modification of alpha-synuclein by processes such as by phosphorylation
and nitration was shown to impair degradation of this protein by a mechanism known as chaperone-mediated autophagy (CMA) in isolated lysosomes, ...
Journal of Alzheimer's Disease special issue explores multifaceted aspects of AD
... processes at the basis of this disease. Several active and passive vaccines against amyloid- humanized antibody, drugs aiming to reduce tau phosphorylation
(GSK3 inhibitors), anti-amyloid-aggregation and anti-APO-E molecules are considered, while the developments of gamma-and beta-secretase inhibitors, ...
ImClone and Bristol-Myers Squibb Announce Joint Agreement With Merck KGaA to Co-Develop and Co-Commercialize ERBITUX(R) in Japan
... growth factor receptor (EGFR, HER1,
c-ErbB-1). In vitro assays and in vivo animal studies have shown that
binding of ERBITUX to the EGFR blocks phosphorylation
and activation of
receptor-associated kinases, resulting in inhibition of cell growth,
induction of apoptosis, and decreased matrix metalloproteinase ...
Brown researchers make major signal transduction discovery
... hepatitis B and C and cancers such as melanoma and leukemia.
This is a major discovery in the field of signal transduction, Chin said. Tyrosine phosphorylation
has so far been considered the major player in signal transduction. But what we discovered challenges this concept. We found another player ...
Pathway links inflammation, angiogenesis and breast cancer
... breast cancer tumors from 116 patients. They found breast cancer patients whose tumors had the TSC1/TSC2 tumor suppressor complex blocked by phosphorylation
did not survive as long as those with an active TSC1/TSC2 (46 percent survival at 60 months vs. 65 percent).
Rapamycin is a powerful immune system ...
Chromatin remodeling complex connected to DNA damage control
... colleagues used a mutant version of Ies4 to mimic constant phosphorylation, more cells were stuck in a checkpoint pause, blocking cell division. When phosphorylation
was blocked, the cells' response to replication stress was impaired, greatly slowing down replication in the absence of another replication ...
Understanding Basic Motor Skills
... a chemical change to the AMPA receptor, called phosphorylation
is necessary for establishing LTD. Mice that ... part of the AMPA receptor which is essential for phosphorylation
do not undergo LTD. This result confirms that phosphorylation
is an essential step toward LTD. Further they ...
Emotional Stress Could Be a Factor in Causing Alzheimers: Study
... restrained mice for half an hour, it resulted only in a transient phosphorylation
of tau. But when they simulated chronic stress by repeating the procedure ... says Sawchenko.
In the absence of CRFR1, stress-induced tau phosphorylation
was abrogated, while in mice missing CRFR2 the effect was amplified, says ...
A new century of Alzheimer's disease research
... may stop tau from initially changing its chemical shape. One design for a therapeutic drug could be to inhibit the molecules involved in the abnormal phosphorylation
of tau, and another might be to find a way to stabilize the microtubules. Amazingly, a cancer drug, Taxol, works to do just that, Dr. Hutton says, ...
Cause of Gender Differences in Blood Pressure, Kidney Damage Under Study
... Just how active an enzyme is depends on how its phosphorylized, or turned on by adding phosphate groups. Our preliminary data says that the phosphorylation
status may increase nitric oxide production - and maintain kidney health - in females, Dr. Sullivan says.
In contrast is the powerful ...
Study Implicates Protein as a Trigger of Advanced Prostate Cancer Recurrence
... by lead author Dr. Nupam P. Mahajan, assistant professor of pharmacology, and other Lineberger scientists. The kinase activates the receptor via phosphorylation
by adding a phosphate group to this protein molecule.
"This biochemical action converts a prostate cell that would need an androgen signal ...
A Novel Target for Type-2 Diabetes Atk2
... investigating whether PGC-1a and Akt2/PKB have the same role in those tissues, says Birnbaum.
The researchers also found that insulin-stimulated phosphorylation
of PGC-1a was blunted in mice that had non-functional Akt2/PKB. Finally, they showed that livers with too much PGC-1a or with PGC-1a that could not ...
Researchers Find New Target to Treat Type 2 Diabetes
... the same role in those tissues, Birnbaum said.
The study also showed that mice that had non-functional Akt2/PKB had low insulin-stimulated phosphorylation
of PGC-1a. The researchers showed that excessive PGC-1a or PGC-1a that could not be phosphorylated cause the liver to produce many copies of the fat ...
New Mechanism for Nutrient Uptake Discovered
... a phosphate molecule is introduced to another molecule, changing the latter, and preparing it for a chemical reaction. They have found a site for phosphorylation
and are looking at this possibility further.
A leading expert in transporters, Professor Dale Sanders, head of the biology department at the ...