Dysregulation of protein phosphorylation plays a major role in many diseases such as cancer and neurodegenerative disorders. In addition, the elucidation of many kinase cascades has proved pivotal for understanding and manipulating cellular behaviour in a variety of divergent eukaryotes.
Within these organisms a wide rage of kinases has been defined. The human genome contains over 500 protein kinase genes, whereas the genome of a small plant like Arabidopsis thaliana, the mouse-ear cress, contains nearly 1,000. Despite this diversity, a team led by Maikel Peppelenbosch, PhD, a professor of Cell Biology at the University Medical Center in Groningen, the Netherlands, has established that all eukaryotic kinases share a common set of substrates, nine amino acid segments shared by all proteins that are known to be phosphorylated.
The team’s work is to be published in the online, open-access journal PLoS ONE on August 22nd.
Using a peptide array, the investigators tested all kinase substrates described in the PhosphoBase phosphorylation database. They incubated them with radio actively labelled ATP as a source of phosphate, and lysates (cell content) of two species of yeast (Candida albicans and Pichia pastoris), a fungus (Fusarium solani), a plant (Triticum aeastivum, wheat), a fruit fly (Drosophila melanogaster), a mouse (Mus musculus), and man (Homo sapiens) as a source of kinases. Their results show that the large diversity of kinases tested is contrasted by a very small diversity in the substrates that are sensitive to them.
These results indicate that, although probably thousands of different kinases have developed during the 2.4 billion years of eukaryotic evolution, they show no significant functional difference. Furthermore, the results suggest the presence of a set of kinase substrates in an ancestral eukaryote that has remained unchanged in eukaryotic life, so the earliest eukaryotes may have been less ‘primitive’ than generally thought.
Since drugs targeting protein kinases are promising for the therapeutic treatment of a host of different diseases, this result may prove to be useful in the testing of such drugs.
The study was funded by the Netherlands Organization for Scientific Research (NOW). Other researchers involved were Sander H. Diks, Kaushal Parikh, and Marijke van der Sijde at the University Medical Center Groningen, Groningen, Jos Joore at Pepscan Presto BV, Lelystad, and Tita Ritsema at the Department of Phytopathology, Utrecht University, Utrecht, all in the Netherlands.
Accordingly, drugs targeting protein kinases are promising avenues for the therapeutic treatment of many different diseases.
Andrew Hyde | alfa
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy