Search results for "PROTEIN KINASE"
showing 10 items of 1188 documents
Early evolution of metazoan serine/threonine and tyrosine kinases: identification of selected kinases in marine sponges.
1997
The phylum Porifera (sponges) was the first to diverge from the common ancestor of the Metazoa. In this study, six cDNAs coding for protein-serine/threonine kinases (PS/TKs) are presented; they have been isolated from libraries obtained from the demosponges Geodia cydonium and Suberites domuncula and from the calcareous sponge Sycon raphanus. Sequence alignments of the catalytic domains revealed that two major families of PS/TK, the "conventional" (Ca(2+)-dependent) protein kinase C (PKC), the cPKC subfamily, as well as the "novel" (Ca(2+)-independent) PKC (nPKC), form two separate clusters. In each cluster, the sequence from S. raphanus diverges first. To approach the question about the or…
Heavy Metals and Metalloids as Autophagy Inducing Agents: Focus on Cadmium and Arsenic
2012
In recent years, research on the autophagic process has greatly increased, invading the fields of biology and medicine. Several markers of the autophagic process have been discovered and various strategies have been reported studying this molecular process in different biological systems in both physiological and stress conditions. Furthermore, mechanisms of metalloid- or heavy metal-induced toxicity continue to be of interest given the ubiquitous nature and distribution of these contaminants in the environment where they often play the role of pollutants of numerous organisms. The aim of this review is a critical analysis and correlation of knowledge of autophagic mechanisms studied under …
A frozen analogue approach to aminopyridinylimidazoles leading to novel and promising p38 MAP kinase inhibitors.
2012
In this study we report the design, synthesis, and biological evaluation of constrained aminopyridinylimidazoles as p38α MAP kinase inhibitors. The frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres as constrained structure analogues. The identification of the most potent bioisostere was followed by a further derivatization to address hydrophobic region II. In combination with C-2 modifications of the imidazole core, we were able to design highly active inhibitors on the p38α MAP kinase. The inhibitor design presented herein represents a promising and highly efficient advancement of recent stages of development in this class of p38 MAP kinase inhibitors. In co…
Modulation of protein phosphorylation by natural products
2002
Studies carried out to determine the influence of phosphorylation and dephosphorylation of proteins in a variety of physiological events are of increasing interest. The activity of kinases and phosphatases and their respective inhibition by endogenous mediators and by pharmacological agents regulates a huge number of biochemical pathways involved in cellular proliferation, apoptosis, inflammation, hormonal activity, and gene transcription, amongother processes. This article focuses on the recently described natural products able to interfere negatively with the activity of serine/threonine and tyrosine kinases. These agents are classified, according to theirbiosynthetic origin and chemical …
Advances in Targeting Signal Transduction Pathways
2012
// James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Lin Sun 1,2 , Nicole M. Davis 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Lucio Cocco 3 , Camilla Evangelisti 4 , Francesca Chiarini 4 , Alberto M. Martelli 3,4 , Massimo Libra 5 , Saverio Candido 5 , Giovanni Ligresti 5 , Grazia Malaponte 5 , Maria C. Mazzarino 5 , Paolo Fagone 5 , Marco Donia 5 , Ferdinando Nicoletti 5 , Jerry Polesel 6 , Renato Talamini 6 , Jorg Basecke 7 , Sanja Mijatovic 8 , Danijela Maksimovic-Ivanic 8 , Michele Milella 9 , Agostino Tafuri 10 , Joanna Dulinska-Litewka 11 , Piotr Laidler 11 , Antonio B. D’Assoro 12 , Lyudmyla Drobot 13 , Kazuo Umezawa 14 , Giuseppe Montalto 15 , Melchiorre Cer…
GSK-3 as potential target for therapeutic intervention in cancer
2014
// James A. McCubrey 1 , Linda S. Steelman 1 , Fred E. Bertrand 2 , Nicole M. Davis 1 , Melissa Sokolosky 1 , Steve L. Abrams 1 , Giuseppe Montalto 3 , Antonino B. D’Assoro 4 , Massimo Libra 5 , Ferdinando Nicoletti 5 , Roberta Maestro 6 , Jorg Basecke 7,8 , Dariusz Rakus 9 , Agnieszka Gizak 9 Zoya Demidenko 10 , Lucio Cocco 11 , Alberto M. Martelli 11 and Melchiorre Cervello 12 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC, USA 2 Department of Oncology, Brody School of Medicine at East Carolina University Greenville, NC, USA 3 Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy …
Repression of Human Papillomavirus Oncogene Expression under Hypoxia Is Mediated by PI3K/mTORC2/AKT Signaling
2019
Oncogenic HPV types are major human carcinogens. Under hypoxia, HPV-positive cancer cells can repress the viral E6/E7 oncogenes and induce a reversible growth arrest. This response could contribute to therapy resistance, immune evasion, and tumor recurrence upon reoxygenation. Here, we uncover evidence that HPV oncogene repression is mediated by hypoxia-induced activation of canonical PI3K/mTORC2/AKT signaling. AKT-dependent downregulation of E6/E7 is only observed under hypoxia and occurs, at least in part, at the transcriptional level. Quantitative proteome analyses identify additional factors as candidates to be involved in AKT-dependent E6/E7 repression and/or hypoxic PI3K/mTORC2/AKT ac…
Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents
2021
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations…
Phosphorylation of cytochrome P450 isoenzymes in intact hepatocytes and its importance for their function in metabolic processes.
1990
Recent data show that besides the well-known long-term regulation of cytochrome P450-dependent monooxygenase activity by induction there also exists a fast regulation by phosphorylation. This phosphorylation occurs when purified cytochromes P450 are combined with purified protein kinases, and also in intact cells. This process is donor- and acceptor-selective leading to phosphorylation of defined isoenzymes by defined protein kinases. This in turn leads to fast and marked changes in metabolism which are selective for given substrates and regio- and stereo-selective for given positions. This in turn is selectively and differentially influenced by the individual control of the protein kinase …
Alterations inras-gene expression and intracellular distribution of protein kinase C in the spongeGeodia cydonium in response to marine pollution
1990
The siliceous spongeGeodia cydonium Jameson was used to study the influence of pollution in marine environments on selected parameters of the intracellular signal transduction pathway. The parameters chosen were: intracellular distribution of protein kinase C (PK-C),ras-gene expression and DNA polymerasealpha (DNA Polalpha) activity. Both PK-C andras-gene product (ras-protein) have previously been established to be key molecules in the intracellular signalling pathway in sponges; increased level ofras-protein mediates events following sponge cell-cell contact. Three unpolluted and three polluted sites in the off-shore seawater around Rovinj (Yugoslavia) were selected for the study in 1989. …