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Researchers unfold the mechanisms underlying blood disorders
Date:7/24/2012

A Finnish research team together with researchers from New York, USA, has uncovered a protein structure that regulates cell signalling and the formation of blood cells. The team's results, published in Nature Structural & Molecular Biology, the most prestigious journal in the field, shed light on the mechanisms at play in haematological disorders and provide new opportunities for the design of disease-specific treatment. The work was carried out with funding from the Academy of Finland, the Cancer Society of Finland, National Institutes of Health and the Sigrid Juslius Foundation.

Blood cell formation and activity is regulated by cytokines, small cell-signalling protein molecules, through a signal pathway mediated by Janus kinases (JAKs), a family of enzymes. Previous studies have shown that mutations in JAKs can cause severe haematological disorders as well as immunological diseases. These mutations are concentrated in the pseudokinase domain.

Leading laboratories and pharmaceutical companies around the world have long aimed at defining the structure of the pseudokinase domain of JAKs, as it has been found to be a veritable hotspot for pathogenic mutations causing haematological disorders. Led by Professor Olli Silvennoinen, the Finnish research team has now successfully determined the three-dimensional atomic-level structure of both the normal and the pathogenic pseudokinase domain.

Novel therapeutics

Professor Silvennoinen's team is the first to describe the structure of the pseudokinase domain of JAKs, laying bare the domain's enzymatic mechanisms at the atomic level. The team also managed to determine the structural change, caused by the JAK2 V617F mutation, which gives rise to common myeloproliferative diseases (MPDs), such as polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). PV and ET are blood disorders characterised by an overproduction of red blood cells or platelets, w
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Contact: Professor Olli Silvennoinen
olli.silvennoinen@uta.fi
358-503-595-740
Academy of Finland
Source:Eurekalert

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