cib1.pdf (1.93 MB)
CIB1 is an endogenous inhibitor of agonist-induced integrin aIIbb3 [alpha II b beta 3]activation
journal contribution
posted on 2009-06-18, 00:00 authored by Weiping Yuan, Tina M Leisner, Andrew W McFadden, Zhengyan Wang, Mark K Larson, Shantres Clark, Christel Boudignon-Proudhon, Stephen CT Lam, Leslie V PariseIn response to agonist stimulation, the alpha IIb beta 3 integrin on platelets is converted to an active conformation that binds fibrinogen and mediates platelet aggregation. This process contributes to both normal hemostasis and thrombosis. Activation of alpha IIb beta 3 is believed to occur in part via engagement of the beta 3 cytoplasmic tail with talin; however, the role of the alpha IIb tail and its potential binding partners in regulating alpha IIb beta 3 activation is less clear. We report that calcium and integrin binding protein 1 (CIB1), which interacts directly with the alpha IIb tail, is an endogenous inhibitor of alpha IIb beta 3 activation; overexpression of CIB1 in megakaryocytes blocks agonist-induced alpha IIb beta 3 activation, whereas reduction of endogenous CIB1 via RNA interference enhances activation. CIB1 appears to inhibit integrin activation by competing with talin for binding to alpha IIb beta 3, thus providing a model for tightly controlled regulation of alpha IIb beta 3 activation.
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Copyright:http://www.jcb.org/misc/copyright.pdfPublisher
Rockefeller University PressLanguage
- en_US
issn
0021-9525Issue date
2006-01-17Usage metrics
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