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CIB1 is an endogenous inhibitor of agonist-induced integrin aIIbb3 [alpha II b beta 3]activation

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Title: CIB1 is an endogenous inhibitor of agonist-induced integrin aIIbb3 [alpha II b beta 3]activation
Author(s): Yuan, Weiping; Leisner, Tina M; McFadden, Andrew W; Wang, Zhengyan; Larson, Mark K; Clark, Shantres; Boudignon-Proudhon, Christel; Lam, Stephen CT; Parise, Leslie V
Subject(s): CIB1, calcium and integrin binding protein 1 cytoplasmic domain calcium-binding protein
Abstract: In 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.
Issue Date: 2006-01-17
Publisher: Rockefeller University Press
Citation Info: Yuan, W. P., T. M. Leisner, A. W. McFadden, Z. Y. Wang, M. K. Larson, S. Clark, C. Boudignon-Proudhon, S. C. T. Lam, and L. V. Parise, 2006, CIB1 is an endogenous inhibitor of agonist-induced integrin alpha IIb beta 3 activation: Journal of Cell Biology, v. 172, no. 2, p. 169-175. http://www.jcb.org.proxy.cc.uic.edu/cgi/content/abstract/172/2/169
Type: Article
Description: Copyright:http://www.jcb.org/misc/copyright.pdf
URI: http://hdl.handle.net/10027/5594
ISSN: 0021-9525
Date Available in INDIGO: 2009-06-18
 

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