The αIIbβ3 integrin, also known as the platelet fibrinogen receptor or GP IIb-IIIa, has been the focus of an entire class of blood-thinning drugs, called GPIIb-IIIa agonists. The Penn researchers findings, published in this week's issue of Science, have implications for drugs created to thin the blood and, perhaps more broadly, offer an intriguing hint as to how integrins on cells throughout the body may function.
"The part of the GPIIb-IIIa molecule that is embedded in the fatty layers that constitute the platelet's outer membrane can determine whether or not the integrin is activated, thereby making the platelet 'sticky,'" said Joel S. Bennett, MD, Professor in Penn's Division of Hematology/Oncology within the Department of Medicine. "The transmembrane region, which was generally assumed to be just an anchor for keeping the integrin receptor in place, can be an activating switch for the entire molecule."
Once activated, the two subunits of GPIIb-IIIa that extend outside the cell can clasp the walls of a damaged blood vessel or a passing fibrinogen molecule V much like a bobby pin can close around strands of hair V thereby forming a normal blood clot or a pathologic thrombus. GPIIb-IIIa agonist drugs, such as ReoPro, Integrilin, and Aggrastat, work by preventing activated GPIIb-IIIa from binding to other objects in the bloodstream.
Since it is a protein, GPIIb-IIIa is made up of amino acids, strung along in a specific sequence to give the protein its shape. Bennett and his colleagues were able
Contact: Greg Lester
University of Pennsylvania School of Medicine