All eukaryotic kinases share 1 common set of substrates

August 21, 2007

Kinase mediated phosphorylation is generally recognised as the major regulator of virtually all metabolic activities in eukaryotic cells including proliferation, gene expression, motility, vesicular transport and programmed cell death. 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.
-end-
Disclaimer


The following press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information. 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.

Citation: Diks SH, Parikh K, van der Sijde M, Joore J, Ritsema T, et al (2007) Evidence for a Minimal Eukaryotic Phosphoproteome". PLoS ONE 2(8):e777. doi:10.1371/journal.pone.0000777

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://www.plosone.org/doi/pone.0000777

PRESS ONLY PREVIEW:http://www.plos.org/press/pone-02-08-diks.pdf

PLOS

Related Genome Articles from Brightsurf:

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Breakthrough in genome visualization
Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome.

Sturgeon genome sequenced
Sturgeons lived on earth already 300 million years ago and yet their external appearance seems to have undergone very little change.

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.

Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.

Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.

A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.

How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.

Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.

Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.

Read More: Genome News and Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.