1992
DOI: 10.1182/blood.v79.5.1233.1233
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High molecular weight kininogen binds to platelets by its heavy and light chains and when bound has altered susceptibility to kallikrein cleavage

Abstract: The unstimulated platelet surface contains a specific and saturable binding site for high molecular weight kininogen (HK) and low molecular weight kininogen (LK). Investigations were performed with purified heavy and light chains of HK to determine which portion(s) of the HK molecule binds to the platelet surface. Purified 64-Kd heavy chain of HK and 56-Kd light chain of HK, independently, inhibited 125I-HK binding to unstimulated platelets with a 50% inhibitory concentration (IC50) of 84 nmol/L (apparent Ki, … Show more

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Cited by 64 publications
(30 citation statements)
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“…The binding of HK to cell surfaces is a crucial step in the kinin‐generating pathway since (i) it assembles two of the three contact phase factors onto endothelial and epithelial linings [1]; (ii) docking to the cell surface protects HK from proteolysis by kallikreins, preventing a constitutive release of bradykinin [10]; (iii) attachment to cell surfaces locates the prohormone in close proximity to its receptors, increasing the probability that short‐lived bradykinin will trigger cellular responses [15]. We have recently identified HS‐type GAG as the major HK docking structures on endothelial cells [11].…”
Section: Discussionmentioning
confidence: 99%
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“…The binding of HK to cell surfaces is a crucial step in the kinin‐generating pathway since (i) it assembles two of the three contact phase factors onto endothelial and epithelial linings [1]; (ii) docking to the cell surface protects HK from proteolysis by kallikreins, preventing a constitutive release of bradykinin [10]; (iii) attachment to cell surfaces locates the prohormone in close proximity to its receptors, increasing the probability that short‐lived bradykinin will trigger cellular responses [15]. We have recently identified HS‐type GAG as the major HK docking structures on endothelial cells [11].…”
Section: Discussionmentioning
confidence: 99%
“…GAGs provide cell‐bound reservoirs of cytokines and other potent hormones that are presented to receptors on target cells [18]. Some cytokines are protected from proteolytic degradation when bound to GAG, as is the case for cell‐bound HK [10]. Furthermore, GAG‐bound cytokines can be detached from cell surfaces by heparin released from mast cells during inflammation [19].…”
Section: Discussionmentioning
confidence: 99%
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“…High-molecular-weight kininogen (HK) binds to platelets in a zinc-dependent reaction, with binding sites demonstrable on domains 3 and 5 (3,4). These same domains have been shown to interact with endothelial cells (6,7) and neutrophils (20) and specific peptides have been identified as the sites of interaction with endothelial cells (6,7).…”
Section: Discussionmentioning
confidence: 99%
“…HK possesses six domains: the first three are homologous to cysteine protease inhibitors, the fourth domain includes the bradykinin moiety, and domains 5 and 6 interact with negatively charged surfaces and with prekallikrein or factor XI, respectively. HK has been shown to bind to platelets by its heavy and light chains (2)(3)(4) and 15-50 ,uM zinc is required for binding. The isolated heavy and light chains derived from kinin-free kininogen can each interact with platelets (4) as well as endothelial cells (5) and those interactions are dependent upon peptides within domains 3 and 5, respectively (6,7).…”
Section: Introductionmentioning
confidence: 99%