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Fibrinogen interaction of CHO cells expressing chimeric αIIb/αvβ3 integrin

  
@article{APS4256,
	author = {Juan-juan Chen and Xiao-yu Su and Xiao-dong Xi and Li-ping Lin and Jian Ding and He Lu},
	title = {Fibrinogen interaction of CHO cells expressing chimeric αIIb/αvβ3 integrin},
	journal = {Acta Pharmacologica Sinica},
	volume = {29},
	number = {2},
	year = {2016},
	keywords = {},
	abstract = {Aim: The molecular mechanisms of the affinity regulation of αvβ3 integrin are important in tumor development, wound repairing, and angiogenesis. It has been established that the cytoplasmic domains of αvβ3 integrin play an important role in integrin-ligand affinity regulation. However, the relationship of structure-function within these domains remains unclear. 
Methods: The extracellular and transmembrane domain of αIIb was fused to the αv integrin cytoplasmic domain, and the chimeric α subunit was coexpressed in Chinese hamster ovary (CHO) cells with the wild-type β3 subunit or with 3 mutant β3 sequences bearing truncations at the positions of T741, Y747, and F754, respectively. The CHO cells expressing these recombinant integrins were tested for soluble fibrinogen binding and the cell adhesion and spreading on immobilized fibrinogen. 
Results: All 4 types of integrins bound soluble fibrinogen in the absence of agonist stimulation, and only the cells expressing the chimeric α subunit with the wild-type β3 subunit, but not those with truncated β3, could adhere to and spread on immobilized fibrinogen.
Conclusion: The substitution αIIb at the cytoplasmic domain with the αv cytoplasmic sequence rendered the extracellular αIIbβ3 a constitutively activated conformation for ligands without the need of “inside-out” signals. Our results also indicated that the COOH-terminal sequence of β3 might play a key role in integrin αIIb/αvβ3-mediated cell adhesion and spreading on immobilized fibrinogen. The cells expressing αIIb/αvβ3 have enormous potential for facilitating drug screening for antagonists either to αvβ3 intracellular interactions or to αIIbβ3 receptor functions.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4256}
}