Cell signaling discovery provides new hope for blood disorders

February 16, 2012

Walter and Eliza Hall Institute scientists have revealed new details about how cell signalling is controlled in the immune system, identifying in the process potential new therapeutic targets for treating severe blood disorders.

Dr Jeff Babon and Professor Nick Nicola, from the institute's and Cancer and Haematology divisions respectively, study interactions between internal cell signalling proteins called JAKs (Janus kinases) and SOCS (Suppressors of Cytokine Signalling).

Dr Babon said the proteins were essential for maintenance and immune responses.

"JAK proteins are activated in response to blood cell hormones called cytokines and instruct to respond to infection and inflammation," Dr Babon said. "SOCS proteins were discovered at the institute in the early 2000s, and provide a necessary 'negative feedback' response that stops JAKs becoming overactive, which can lead to disease."

Dr Babon said mutations in one particular protein, , are strongly associated with the development of myeloproliferative diseases.

"When JAK2 is mutated, it tells cells to continually multiply. An excessive amount of blood cells of one type are produced, and the bone marrow is overrun, leading to problems with production of other cell types, and eventually ," Dr Babon said.

Myeloproliferative diseases, such as polycythemia vera and essential thrombocytopenia, are serious in which an excessive number of accumulate in the bone marrow. They can be very severe and sometimes fatal, and may progress to acute leukaemias.

In a study published today in the journal Immunity, Dr Babon and Professor Nicola, with colleagues Dr James Murphy and Dr Nadia Kershaw, report on a key discovery about how the proteins JAK2 and SOCS3 interact. They hope the discovery will lead to new strategies for treating myeloproliferative diseases.

"SOCS3 is a key inhibitor of JAK2 proteins in blood and immune cells, but we didn't know exactly how the two proteins interacted to suppress JAK2 function," Dr Babon said. "We wanted to identify which site the SOCS3 protein bound to on the JAK2 protein to inhibit its action, and were surprised to find that SOCS3 binds to a unique site on JAK2 and directly inhibits the protein, rather than outcompeting other molecules."

Dr Babon said the finding could inspire a new class of therapeutic agents for treating myeloproliferative diseases.

"The SOCS3 binding site is a previously unknown part of the JAK2 protein which could be exploited as a drug target, with greater specificity than other drugs that are currently in clinical trials for inhibiting JAK2," he said.

Explore further: Genetic finding offers hope for orphan disease

Related Stories

Recommended for you

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.