January 31, 2013, New York, NY and Brussels, Belgium Clear communication between cells is essential to every aspect of the body's internal function. But since cells can't talk, or send emails, how do they communicate?
The answer, in a nutshell, is by dispatching signaling molecules that selectively bind to protein receptors on the outer surface of other cells with which they must "talk." This activates the tail end of such receptors inside the cell, initiating a cascade of enzymatic reactions, or signaling pathways that reach into the nucleus, turning genes on and off. All such signaling is tightly regulated, and mutations that permanently activate certain receptors can drive the uncontrolled proliferation of cells, a defining characteristic of cancers.
In a paper published this week in the Proceedings of the National Academy of Sciences, a team led by Ludwig researcher Stefan Constantinescu, MD PhD, in Brussels based at the de Duve Institute, Universit catholique de Louvain and Steven Smith, PhD, of Stony Brook University in New York shows how a mutation that alters a single amino acid in the thrombopoietin receptor turns it on permanently, explaining how it leads to the blood malignancies essential thrombocythemia (ET) and primary myelofibrosis.
"The thrombopoietin receptor is important in hematopoiesis, or the formation of blood," says Constantinescu. "It is activated by a factor known as thrombopoietin, and is required for the wellbeing of stem cells in the bone marrow and the generation of platelets, which are involved in clotting." A mutation that continuously turns on the signaling pathway it controls has been shown to lead to certain kinds of blood cancer. But some forms of ET and primary myelofibrosis do not bear that mutation.
In 2006, Constantinescu's lab identified a unique chain of five amino acids at the bottom of a coiled portion of the thrombopoietin receptor (TpoR) that traverses the membrane. The
|Contact: Rachel Steinhardt|
Ludwig Institute for Cancer Research