A5025815250- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Cell death mechanisms and regulation
- Cytokine Signaling Pathways and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Protein Tyrosine Phosphatases
- NF-κB Signaling Pathways
- Endoplasmic Reticulum Stress and Disease
- Cellular Mechanics and Interactions
- Cancer, Hypoxia, and Metabolism
- Synthesis and biological activity
- Autophagy in Disease and Therapy
- Immune Response and Inflammation
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Pancreatic and Hepatic Oncology Research
- Metabolism, Diabetes, and Cancer
- Protein Degradation and Inhibitors
Babraham Institute
2015-2024
University of Dundee
2018-2024
Murdoch University
2022-2023
Australian Research Council
2022
ARC Centre of Excellence for Electromaterials Science
2022
Swinburne University of Technology
2022
Federation University
2022
Royal Victoria Infirmary
2021
Manchester Metropolitan University
2014-2016
Laboratory of Molecular Genetics
2011
Activation of the Raf and extracellular signal-regulated kinases (ERKs) (or mitogen-activated protein kinases) are key events in mitogenic signaling, but little is known about interactions with other signaling pathways. Agents that raise levels intracellular cyclic adenosine 3′,5′-monophosphate (cAMP) blocked DNA synthesis signal transduction Rat1 cells exposed to epidermal growth factor (EGF) or lysophosphatidic acid. In case EGF, receptor tyrosine kinase activity association molecules Grb2...
Both the ERK and phosphatidylinositol 3′-kinase (PI3K) signaling pathways can protect cells from apoptosis following withdrawal of survival factors. We have previously shown that ERK1/2 pathway acts independently PI3K to block expression BH3-only protein, BimEL, prevent serum withdrawal-induced cell death, although precise mechanism by which reduced BimEL levels was unclear. By comparing Bim mRNA we now show rapid cannot be accounted for simply increases in inhibition PI3K. In maintained is...
We previously reported the cloning of a cDNA encoding human phosphatidylcholine-specific phospholipase D1 (PLD1), an ADP-ribosylation factor (ARF)-activated D (Hammond, S. M., Tsung, S., Autschuller, Y., Rudge, A., Rose, K., Engebrecht, J., Morris, A. and Frohman, M. (1995) J. Biol. Chem. 270, 29640-29643). have now identified evolutionarily conserved shorter splice variant PLD1 lacking 38 amino acids (residues 585-624) that arises from regulated splicing alternate exon. Both forms (PLD1a...
Cells must adapt to changes in their environment maintain cell, tissue and organismal integrity the face of mechanical, chemical or microbiological stress. Nuclear factor-κB (NF-κB) is one most important transcription factors that controls inducible gene expression as cells attempt restore homeostasis. It plays critical roles immune system, from acute inflammation development secondary lymphoid organs, also has cell survival, proliferation differentiation. Given its role such processes,...
Abstract The microtubule-targeting compound paclitaxel is often used in the treatment of endocrine-resistant or metastatic breast cancer. We have previously shown that apoptosis cancer cells response to mediated by induction FOXO3a expression, a transcription factor downstream phosphatidylinositol-3-kinase/Akt signaling pathway. To further investigate its mechanism action, we treated MCF-7 with and showed dose-dependent increase nuclear localization FOXO3a, which coincided decreased Akt but...
Resistance to cancer therapeutics targeting the second kinase in a three-kinase cascade involves amplification of upstream kinase, not inhibited kinase.
Bim, a "BH3-only" protein, is expressed de novo following withdrawal of serum survival factors and promotes cell death. We have shown previously that activation the ERK1/2 pathway phosphorylation Bim(EL), targeting it for degradation via proteasome. However, nature kinase responsible Bim(EL) remained unclear. now show phosphorylated on at least three sites in response to pathway. By using peptidylprolyl isomerase, Pin1, as probe proline-directed phosphorylation, we ERK1/2-dependent occurs...
The role of protein kinase C (PKC) in inflammation, mitogenesis, and differentiation has been deduced part through the use a variety PKC inhibitors. Two widely used inhibitors are structurally related compounds GF109203X Ro-31-8220, both which potently inhibit activity believed to be highly selective. While using Ro-31-8220 address immediate early gene expression, we observed striking differential effects by each these two compounds. Growth factors induce expression products MAP...
A method for the rapid and quantitative separation of glycerophosphocholine, choline phosphate upon ion-exchange columns is described. The has been utilized to examine stimulation phosphatidylcholine breakdown in quiescent Swiss 3T3 cells response bombesin 12-O-tetradecanoylphorbol 13-acetate (TPA). stimulated generation shown precede that phosphate, with no effect glycerophosphocholine levels; but was attenuated which protein kinase C activity down-regulated. results thus suggest either or...
Host-pathogen interactions that allow Helicobacter pylori to survive and persist in the stomach of susceptible individuals remain unclear. Human beta-defensins (hBDs), epithelial-derived antimicrobial peptides are critical components host-defense at mucosal surfaces. The role H. pylori-mediated NF-kappaB epidermal growth factor receptor (EGFR) activation on beta-defensin expression was investigated. Transient transfection studies utilizing promoter constructs were conducted gastric cells...
Genome-wide erasure of DNA methylation takes place in primordial germ cells (PGCs) and early embryos is linked with pluripotency. Inhibition Erk1/2 Gsk3β signalling mouse embryonic stem (ESCs) by small molecule inhibitors (called 2i) has recently been shown to induce hypomethylation. We show whole-genome bisulphite sequencing that 2i induces rapid genome-wide demethylation on a scale pattern similar migratory PGCs embryos. Major satellites, intracisternal A particles (IAPs) imprinted genes...
Progression through the stages of lymphocyte development requires coordination cell cycle. Such ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands pools progenitor lymphocytes. Here we show that in developing B lymphocytes, RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor (pre-BCR)...