The Platelet Membrane Glycoprotein IIb/IIIa Complex

Abstract

The GPIIb/IIIa complex functions as the aggregation site on the platelet membrane surface. This complex has been purified, characterized biochemically and morphologically, and reconstituted into phospholipid vesicles. Fibrinogen and fibronectin bind to reconstituted GPIIb/IIIa with many of the properties that characterize their binding to intact platelets. The GPIIb/IIIa complex appears to be a member of a widely distributed family of cell-surface glycoproteins that mediate cellular interactions. The terms cytoadhesins30 and integrins39 have been suggested for the members of this family of two-subunit molecules. The aminotermini of the alpha subunits of these molecules have been sequenced and appear to be homologous. Three beta subunits have been identified for this family of receptors, indicating that many alpha subunits have a common beta subunit. The three beta subunits have been sequenced, and there is about a 40 to 50% identity among their amino acid sequences. It thus appears that the receptors mediating cellular interactions have evolved from a common ancestral gene.

Adhesion of T and B lymphocytes to extracellular matrix and endothelial cells can be regulated through the beta subunit of VLA

“…This has now been demonstrated for the ~ (Nojima et al, 1990),/32 (Van Kooyk et al, 1989Dustin and Springer, 1989), and/33 (O'Toole et al, 1990) group of this adhesion receptor family. PMA has been recognized to induce/32-mediated adhesion (Patarroyo et al, 1985;Springer, 1990),/33-mediated adhesion (Phillips et al, 1988), and more recently also /31-mediated adhesion (Shimizu et al, 1990).…”

“…This has now been demonstrated for the/31 (Shimizu et al, 1990),/32 (Van Kooyk et al, 1989;Dustin and Springer, 1989), and 133 (O'Toole et al, 1990) group of this adhesion receptor family. Phorbol esters, such as PMA, are able to induce a high affinity state of the/31, 152, and 133 integrins (Patarroyo et al, 1985;Phillips et al, 1988;Shimizu, 1990;Springer, 1990;Wilkins et al, 1991). In addition, a number of more physiological stimulatory pathways have been recognized to stimulate integrin-mediated adhesion.…”

“…Other groups of this still expanding family comprise the /~2, or leukocyte integrin group (Sanchez-Madrid et al, 1983), and thb/$3 group, which consists of the platelet antigen IIb/IIIa (Phillips et al, 1988) and the vitronectin receptor (Pytela et al, 1985). The VLA molecules mediate adhesion of cells with components of the extracellular matrix (ECM) (Hemler, 1990).…”

Biogenesis of endoplasmic reticulum proteins involved in Ca2+ signalling during megakaryocytic differentiation: an in vitro study

“…Electrophoresis was performed at 140 V for 1 h and proteins were electrotransferred on to nitrocellulose membranes. The membranes were then treated for 2 h at room temperature with 1 µg\ml of the monoclonal anti-SERCA3 PL\IM430 antibody (a monoclonal anti-Ca# + -ATPase antibody raised against highly purified platelet intracellular membranes as immunogen) [32], 1 : 1000 dilution of the monoclonal anti-SERCA2 IID8 [33] and anti-InsP $ -R type-III [34] antibodies, 1 : 1000 dilution of the polyclonal anti-InsP $ -R type-I [35] antibody, or 1 : 5000 dilution of the polyclonal anti-glycoprotein IIIa (GPIIIa) [36] and anticalreticulin [37] antibodies. Thereafter, the nitrocellulose sheets were washed extensively and further incubated with a 1 : 2000 dilution of the anti-mouse IgG horseradish peroxidase conjugate for immunostaining of the monoclonal antibodies and a 1 : 10 000 dilution of the anti-rabbit IgG horseradish peroxidase conjugate for immunostaining of polyclonal antibodies, for 1.5 h. After washing, antibody binding was detected using ECL Westernblotting reagents according to the manufacturer's instructions.…”

Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen

“…Fibrinogen is a key protein involved in blood coagulation and hemostasis (Liu et al, 1979;Phillips et al, 1988;Sidelmann et al, 2000). Both the amount (physiological concentrations normally range from 1.5 mg/mL to 4 mg/mL in human blood) and the activity of fibrinogen are important for maintaining the equilibrium of coagulation (Kamath and Lip, 2003).…”