( Calling it an important technical advan...)UCSD researchers create roadmap to integrin activation

Calling it an important technical advance in the study of the complex receptors and pathways of the body's cellular system, researchers at the University of California, San Diego (UCSD) School of Medicine have reconstructed the signaling pathways that impact activation of a receptor that is critical to the control of bleeding and to the thrombosis that occurs in heart attacks and strokes.

Their work to take apart and re-build the signaling pathway that regulates activation of the body's most abundant platelet receptor, an integrin called glycoprotein (GP) IIb-IIIa, provides a powerful and flexible tool for studying therapeutic targets along the pathway that impacts the activation process. This activation leads to changes in the cells' surface receptors ?changes that enable platelets to bind to the wall of blood vessels and to one another.

"The road map of the activation pathway could lead to the development of new antithrombotic drugs or treatments for inflammatory diseases. In addition, the ability to engineer these activation pathways may contribute to efforts to develop artificial platelets or leukocytes that could be used in patients with suppressed bone marrow function, for example," said Mark H. Ginsberg, M.D., professor of Medicine at the UCSD School of Medicine. The study will be published on line in Current Biology on September 19.

Integrins are a large family of adhesion molecules that promote stable interactions between cells and their environment. The integrins also act as cellular sensor and signaling molecules, transferring information between the inside and outside of a cell at plasma membrane sites.

Platelets stop the body's bleeding by sticking to one another. When a patient experiences a heart attack or stroke, the platelets stick inappropriately, clumping together and blocking the blood vessel. A signal from inside the platelet to the outside tells the GPIIb-IIIa integrin on the cell's surface to get sticky.
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Source:University of California - San Diego

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