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A switch that makes a blood clot sticky found within the platelet membrane

to determine which amino acids are responsible for activating GPIIb-IIIa by substituting a 'wrong' amino acid at spaces along the  protein chain and expressing the mutant protein in cells growing in culture. They found that the transmembrane portion of one of the GPIIb-IIIa subunits is responsible for responding to activation signals and, in return, causing groups of the activated integrin to cluster.

"Remarkably, these regions are evolutionarily conserved V meaning the transmembrane region in GPIIb-IIIa is the same in apes or rabbits or mice as they are in humans," said Bennett. "That tells us that the sequences of the transmembrane region of integrins are important factors in how these proteins function."

Moreover, nearly every integrin has a different transmembrane region made up of a unique amino acid sequence. If the transmembrane regions of all integrins work on a similar scheme, it would provide a new paradigm for the function of integrins and other cell membrane proteins.

"Integrin receptors are more than just a cellular form of Velcro V as integrins bind, they can also generate signals that command a cell to act, such as whether to divide or differentiate or to produce an important protein such as a gene transcription factor," said Bennett. "It will be interesting, and even medically important, to determine how these signals can be modulated."

Other scientists involved in the research paper described here include Renhao Li, Neal Mitra, Holly Gratkowski, Gaston Vilaire, Reustem Litvinov, Chandrasekaran Nagasami, John Weisel, James D. Lear, and William F. DeGrado from Penn.


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Contact: Greg Lester
lesterg@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
1-May-2003


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