2001
DOI: 10.1021/bi002902i
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Mechanism of Integrin Activation by Disulfide Bond Reduction

Abstract: Integrin alphaIIbbeta3 plays a pivotal role in hemostasis and thrombosis by mediating platelet adhesion and platelet aggregation. Integrin alphaIIbbeta3 contains an on/off switch that regulates its ligand binding affinity. The switch from "off" to "on" is commonly referred to as integrin activation. We recently identified a redox site within the extracellular domain of the platelet integrin alphaIIbbeta3 that exhibits many properties that one might expect of the on/off switch [Yan, B., and Smith, J. W. (2000) … Show more

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Cited by 121 publications
(104 citation statements)
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References 33 publications
(49 reference statements)
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“…Mild reducing conditions have been shown to be sufficient to bring about integrin activation, the process by which the integrin ligand binding site is uncovered and its affinity increased (66). ␤ 3 integrins, especially ␣ IIb ␤ 3 , were especially sensitive to activation by reducing conditions, since they contain a redox site within the extracellular domain, and sustained activation of ␤ 3 -containing heterodimers required reduction of extracellu-lar free sulfhydryls and disulfide exchange (67,68).…”
Section: Discussionmentioning
confidence: 99%
“…Mild reducing conditions have been shown to be sufficient to bring about integrin activation, the process by which the integrin ligand binding site is uncovered and its affinity increased (66). ␤ 3 integrins, especially ␣ IIb ␤ 3 , were especially sensitive to activation by reducing conditions, since they contain a redox site within the extracellular domain, and sustained activation of ␤ 3 -containing heterodimers required reduction of extracellu-lar free sulfhydryls and disulfide exchange (67,68).…”
Section: Discussionmentioning
confidence: 99%
“…Expression of free sulfhydryls on the extracellular domain of the purified platelet integrin ␣ IIb ␤ 3 in its active conformation was recently demonstrated. 9,18,19 The expression of PDI activity on the surface of cells, including platelets, 20,21 indicates the importance of disulfide exchange on the surface of cells in general and platelets in particular. Furthermore, inhibition of PDI was found to block agonist-induced platelet aggregation.…”
Section: Introductionmentioning
confidence: 99%
“…This reaction has been extensively studied and is known to be important in the function and folding processes of proteins (8)(9)(10). This reaction is also of particular interest because it is known that many proteins that are exposed to mechanical stress in vivo contain disulfide bonds (11)(12)(13). Thus, the effect of force on this reaction could be of significance in biological systems.…”
mentioning
confidence: 99%