In:
Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 90, No. 09 ( 2003), p. 465-475
Abstract:
Agglucetin, a tetrameric agglutination inducer from the Formosan pit viper, has been identified as a platelet membrane glycoprotein (GP) Ib agonist and directly agglutinated fixed-platelets in the absence of von Willebrand factor (vWf). Here, we resolved the complete cDNA sequences of agglucetin subunits (α1, α2, β1 and β2) by molecular cloning. Each cloned cDNA encoding the leader peptide (23 residues) and the mature subunit (131/135/123/126 residues) shares a high degree of homology to each other and the C-type lectin-like GP Ib-binding proteins (BPs). Furthermore, agglucetin specifically caused platelet agglutination and surface exposure of integrin αIIbβ3 with a GPIb-dependent manner in washed platelets, based on the observation that the enhanced expression of functional αIIbβ3 was suppressed by a GPIb-cleaving metalloproteinase, crotalin. Pretreating platelets with staurosporine or BAPTA-AM also completely blocked the exposure of functional αIIbβ3, suggesting that the activation of protein kinase C and intracellular calcium mobilization are involved in the GPIb-dependent signaling. In human platelet-rich plasma (PRP), agglucetin elicited sequential biphasic responses of platelet agglutination and aggregation in a GPIb- and αIIbβ3-dependent manner, respectively, implying that other cofactors may amplify platelet activation to trigger aggregation. The nucleotide sequences reported in Figs. 1 and 2 have deposited in the GenBank, EMBL and DDBJ Nucleotide Sequence Databases under the accession numbers: AF540645 for agglucetin-α1 subunit, AF540646 for agglucetin-α2 subunit, AF540647 for agglucetin-β1 subunit and AF540648 for agglucetin-β2 subunit.
Type of Medium:
Online Resource
ISSN:
0340-6245
,
2567-689X
DOI:
10.1160/TH03-02-0072
Language:
English
Publisher:
Georg Thieme Verlag KG
Publication Date:
2003
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