A5071181577- Protein Kinase Regulation and GTPase Signaling
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- PI3K/AKT/mTOR signaling in cancer
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Cellular transport and secretion
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Telomeres, Telomerase, and Senescence
- RNA and protein synthesis mechanisms
- Platelet Disorders and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Animal Genetics and Reproduction
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Cell Adhesion Molecules Research
- Protein Tyrosine Phosphatases
- Carcinogens and Genotoxicity Assessment
- Wnt/β-catenin signaling in development and cancer
University of Reading
2003-2022
Technion – Israel Institute of Technology
1999-2012
Tel Aviv Sourasky Medical Center
2010
University of California, Davis
2007
Institute of Cancer Research
1977-2001
University of Washington
1984-2000
Breast Cancer Now
1998-1999
Environmental Protection Agency
1998
Israel Institute
1994
Ludwig Cancer Research
1991-1994
The VPS 34 gene product (Vps34p) is required for protein sorting to the lysosome-like vacuole of yeast Saccharomyces cerevisiae . Vps34p shares significant sequence similarity with catalytic subunit bovine phosphatidylinositol (PI) 3-kinase [the 110-kilodalton (p110) PI 3-kinase], which known interact activated cell surface receptor tyrosine kinases. Yeast strains deleted or carrying vps point mutations lacked detectable activity and exhibited severe defects in vacuolar sorting....
The fragile X mental retardation syndrome is associated with the expansion of trinucleotide 5'-d(CGG)-3' repeats within FMR1 gene and hypermethylation cytosine residues these repeats. may account for suppression transcription delay its replication during cell cycle. Here we show that d(CGG)n oligomers can form a stable Hoogsteen-bonded structure exhibits properties consistent those tetraplex DNA. Oligomers, d(mCGG)n, (n = 4, 5, or 7), at pH 8.0 in presence an alkali metal ion species...
Werner Syndrome (WS) is a human progeroid disorder characterized by genomic instability. The gene defective in WS encodes 3′ → 5′ DNA helicase (Gray, M. D., Shen, J.-C., Kamath-Loeb, A. S., Blank, A., Sopher, B. L., Martin, G. M., Oshima, J., and Loeb, L. A.(1997) Nat. Genet. 17, 100–103). Sequence alignment analysis identified an N-terminal motif WRN that homologous to several exonucleases. Using combined molecular genetic, biochemical, immunochemical approaches, we demonstrate also...
In addition to its DNA helicase activity, Werner syndrome protein (WRN) also possesses an exonuclease activity (Shen, J.-C., Gray, M. D., Kamath-Loeb, A. S., Fry, M., Oshima, J., and Loeb, L. (1998) J. Biol. Chem. 273, 34139-34144). Here we describe the properties of nearly homogeneous WRN exonuclease. hydrolyzes a recessed strand in partial duplex but does not significantly digest single-stranded DNA, blunt-ended duplex, or protruding duplex. Although is hydrolyzed absence nucleoside...
Werner syndrome (WS) is an inherited disorder characterized by premature aging and genomic instability. The protein encoded the WS gene, WRN, possesses intrinsic 3′ → 5′ DNA helicase exonuclease activities. WRN resolves alternate structures including tetraplex triplex DNA, Holliday junctions. Thus, one function of may be to unwind secondary that impede cellular transactions. We report here hairpin G′2 bimolecular fragile X expanded sequence, d(CGG)n, effectively synthesis three eukaryotic...
Human platelets undergo a rapid, major reorganization of the cytoskeletal matrix upon exposure to thrombin, and accumulate 3-phosphorylated phosphoinositides in protein kinase C (PKC)-dependent manner. These have been suggested be involved actin polymerization/depolymerization. We reasoned that, if newly generated phosphoinositide modulates reorganization, prerequisite for such action would generation near proteins. found after platelet activation, phosphatidylinositol 3-kinase...
Two DNA polymerases that can copy synthetic RNA polymers are present in human tissue culture cells. These enzymes which have each been purified about 500-fold, both HeLa cells, derived from a cervical carcinoma, and WI-38 normal diploid strain originating embryonic lung tissue. RNA-dependent identified by their ability to efficiently the ribo strand of oligonucleotide-homopolymer complexes, differ this respect known DNA-dependent found The template requirements these new resemble tumor-viruses.
Objective— Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling suspension; however, significance this observation how it relates to unclear, as platelets encounter immobile collagen vivo. We sought clarify effects ibrutinib on...
The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many cellular responses such as proliferation, migration, and survival. Disregulation PI3K-activated pathways is implicated different diseases including cancer diabetes. Among the three classes PI3Ks, class I best characterized, whereas II has received increasing attention only recently precise role these isoforms unclear. Similarly, phosphatidylinositol-3-phosphate (PtdIns-3-P) an intracellular second messenger just...
The interaction between SH2 domains and phosphotyrosine-containing sequences was examined by real-time measurements of kinetic parameters. the p85 subunit phosphatidylinositol 3-kinase as well other signaling molecules were expressed in bacteria glutathione S-transferase fusion proteins. Phosphotyrosine-containing peptides, corresponding to two autophosphorylation sites on human platelet-derived growth factor beta-receptor that are responsible for binding, synthesized used capturing...