A5090700145- Protein Kinase Regulation and GTPase Signaling
- PI3K/AKT/mTOR signaling in cancer
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- Cytokine Signaling Pathways and Interactions
- Protein Tyrosine Phosphatases
- RNA Research and Splicing
- Nuclear Structure and Function
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Glycosylation and Glycoproteins Research
- Cancer-related gene regulation
- Computational Drug Discovery Methods
- Liver physiology and pathology
- Melanoma and MAPK Pathways
Semmelweis University
2015-2025
HUN-REN Research Centre for Natural Sciences
2016-2025
Institute of Molecular Life Sciences
2014-2023
Eötvös Loránd University
2022
Institute of Biochemistry
1986-2021
Hungarian Academy of Sciences
2011-2020
Budapest University of Economics and Business
2020
Royal Canadian Navy
2014
The Honourable Society of Lincoln's Inn
1993-2003
Cancer Research UK
2003
T lymphocytes contain both Grb2, an SH2 and SH3 domain containing adaptor protein, Sos, a guanine nucleotide exchange factor for Ras. Immunoprecipitates of Sos from the lysates cells 36-kDa protein which is phosphorylated on tyrosine residues in response to cell receptor/CD3 cross-linking. In vitro studies using different bacterially synthesized GST-Sos fusion proteins confirm formation complexes p36 proline-rich COOH-terminal Sos. The use mutant GST-Grb2 domains have been mutationally...
Abstract Iressa (ZD1839, Gefitinib), used in clinics to treat non–small cell lung cancer patients, is a tyrosine kinase receptor inhibitor that leads specific decoupling of epidermal growth factor (EGFR) signaling. Recent data indicate especially effective tumors with certain EGFR mutations; however, subset these does not respond Iressa. In addition, populations have an elevated risk side effects during treatment. The human ABCG2 (BCRP/MXR/ABCP) transporter causes drug resistance by actively...
Shc proteins are phosphorylated on tyrosine residues and associate with growth factor receptor-bound protein 2 (Grb2) upon treatment of cells epidermal (EGF) or insulin. We have studied the role in insulin- EGF-induced activation p21ras NIH 3T3 overexpressing human insulin receptors (A14 cells). A14 equally responsive to EGF respect p21ras. Analysis immunoprecipitates revealed that (i) both resulted phosphorylation (ii) antibodies coimmunoprecipitated Grb2 mSOS after treatment. The induction...
Several pleckstrin-homology (PH) domains with the ability to bind phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3, PIP3] were expressed as green fluorescent protein (GFP) fusion proteins determine their effects on various cellular responses known be activated by PIP3. These comprised PH of Akt, ARNO, Btk or GRP1, and found show growth-factor-stimulated wortmannin-sensitive translocation from cytosol plasma membrane in several cell types, indicating recognize Remarkably, although...
Several recent studies have demonstrated that Grb2, composed entirely of SH2 and SH3 domains, serves as an adaptor protein in tyrosine kinase signaling pathways. Cbl, the product c-cbl proto-oncogene, has been reported to be phosphorylated on residues upon T cell receptor (TCR) engagement. Here we show unstimulated Jurkat cells Cbl is co-immunoprecipitated with monoclonal antibody against Grb2. However, lymphocytes activated through TCR, loses its ability bind Grb2 precipitated either...
Treatment of intact Rat-1 fibroblasts with epidermal growth factor (EGF) leads to rapid activation cellular ras-encoded proteins. By using the bacterial toxin streptolysin O permeabilize these cells, it was shown that low basal rate at which guanine nucleotides bind to, and dissociate from, protein in quiescent greatly accelerated by EGF treatment. Nucleotide binding other proteins not affected. Stimulation nucleotide exchange on required tyrosine kinase but phospholipase activity. had no...
Vav2 is a member of the Vav family that serves as guanine nucleotide exchange factor for Rho Ras-related GTPases. Unlike Vav1, whose expression restricted to cells hematopoietic origin, broadly expressed. Recently, has been identified substrate epidermal growth (EGF) receptor; however, mechanism by which activated in EGF-treated unclear. By means an <i>in vitro</i> protein kinase assay, we show here purified and EGF receptor phosphorylates exclusively on its N-terminal domain. Furthermore,...
Chromosomal translocations, which often generate chimeric proteins by fusing segments of two distinct genes, represent the single major genetic aberration leading to cancer. We suggest that unifying theme these events is a high level intrinsic structural disorder, enabling fusion evade cellular surveillance mechanisms eliminate misfolded proteins. Predictions in 406 translocation-related human show they are significantly enriched disorder (43.3% vs. 20.7% all proteins), have fewer Pfam...
Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of primary reasons gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, activated play a role during invasion, but signaling cascades remained unknown. Here we utilised knockout lines derived from fibronectin-/-, integrin-beta1-/-, focal adhesion kinase (FAK)-/- Src/Yes/Fyn-/- deficient mice, wild-type...
The Nck adaptor protein links tyrosine kinases or their substrates to proteins containing proline-rich motifs. Here we show that in activated T cells two phosphoproteins of 75 and 120 kDa are co-immunoprecipitated with polyclonal antibodies against Nck. Analysis immunoprecipitates various candidate revealed the 75-kDa phosphoprotein is SH2 domain-containing leukocyte referred as SLP-76. In vitro experiments interaction between SLP-76 mediated via domain. Using specific phosphopeptides...
In T lymphocytes activated via the cell antigen receptor (TCR), SH2- and SH3-containing adapter molecule Grb2 forms a complex with Ras guanine nucleotide exchange protein Sos tyrosine phospho-proteins. The interaction of is mediated SH3 domains. this study, it shown that 75-kDa also complexed domains in cells, but not Rat-1 fibroblasts. identity p75 known, immunoblot analysis phosphotyrosine antibodies indicated rapidly tyrosine-phosphorylated TCR-activated cells. This characteristic clearly...
CASK-interactive protein1 is a newly recognized post-synaptic density protein in mammalian neurons. Although its N-terminal region contains several well-known functional domains, entire C-terminal proline-rich of 800 amino acids lacks detectable sequence homology to any previously characterized protein. We used multiple techniques for the structural characterization this and three fragments. By bioinformatics predictions, CD spectroscopy, wide-line 1H-NMR limited proteolysis gel filtration...