Platelet factor XI is associated with the platelet plasma membrane and has an apparent M r (220,000 nonreduced, 55,000 reduced) different from that of plasma factor XI. However, the site of synthesis and the nature of platelet factor XI are not known. Using reverse transcriptase polymerase chain reaction, 12 out of 13 exons (all except exon V) coding for mature plasma factor XI were amplified from human platelet mRNA. The sequence of each of these exons was identical to that of plasma factor XI. In situ amplification and hybridization of factor XI mRNA was positive for exon III and negative for exon V in platelets and negative for both exons in other blood cells. By Northern hybridization, a factor XI mRNA transcript of ϳ1.9 kilobases was detected in megakaryocytic cells, and one of ϳ2.1 kilobases was detected in liver cells. Factor XI cDNA was cloned from a megakaryocyte library and sequenced. Exon V was absent, and the splicing of exon IV to exon VI maintained the open reading frame without alteration of the amino acid sequence except for the deletion of amino acids Ala 91 -Arg 144 within the amino-terminal portion of the Apple 2 domain. Thus, platelet factor XI is an alternative splicing product of the factor XI gene, localized to platelets and megakaryocytes but absent from other blood cells.Plasma coagulation factor XI is a glycoprotein present in human plasma at a concentration of ϳ30 nM as a zymogen that, when converted by limited proteolysis to an active serine protease, participates in the contact phase of blood coagulation. This zymogen is an unique plasma coagulation enzyme because it exists as a homodimer (M r ϳ143,000) consisting of two identical polypeptide chains linked by disulfide bonds (1, 2).The sequence of the human factor XI gene has been elucidated by sequencing of the cDNA inserts coding for factor XI from two different phage genomic libraries (3,4 Factor XI coagulant activity and antigen are present in wellwashed platelet suspensions, and the activity accounts for about 0.5% of the total factor XI activity in blood (5, 6). About half of factor XI-deficient patients have defective hemostasis, whereas the remainder do not experience abnormal bleeding even in the absence of plasma factor XI (7). Subcellular fractionation studies have shown that factor XI activity is enriched in the platelet membrane fraction (8). The washed platelets and isolated platelet membranes obtained from a factor XIdeficient donor without a history of excessive bleeding had normal quantities of factor XI-like activity and normal behavior in the contact phase of coagulation (9). Thus, the functional significance of factor XI associated with platelets is not clear, but it may play a role in maintaining normal hemostasis, possibly complementing plasma factor XI deficiency (9).Previous studies employing immunofluorescence, immunoelectrophoresis, and immunoprecipitation utilizing monospecific polyclonal anti-factor XI antibodies have demonstrated the presence in and partial purification from human platelets of a molecule ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.