Complex Formation of Platelet Membrane Glycoproteins IIb and IIIa: A Model of Platelet Activation

2015 ◽  
pp. 127-130
Author(s):  
Ralph L. Nachman ◽  
Margaret Polley ◽  
Lawrence L. K. Leung
Keyword(s):  
Complex Formation ◽  
Platelet Activation ◽  
Platelet Membrane ◽  
Membrane Glycoproteins

scholarly journals Complex formation of platelet membrane glycoproteins IIb and IIIa with the fibrinogen D domain.

1984 ◽  
Vol 259 (13) ◽  
pp. 8584-8588 ◽  
Author(s):  
R L Nachman ◽  
L L Leung ◽  
M Kloczewiak ◽  
J Hawiger
Keyword(s):  
Complex Formation ◽  
Platelet Membrane ◽  
Membrane Glycoproteins

Effects of Thrombin, Chymotrypsin and Aggregated Gamma-Globulins on the Proteins of the Human Platelet Membrane

1977 ◽  
Vol 37 (03) ◽  
pp. 396-406 ◽  
Author(s):  
B Podolsak
Keyword(s):  
Molecular Weight ◽  
Platelet Activation ◽  
Gel Electrophoresis ◽  
Human Platelet ◽  
Polyacrylamide Gel Electrophoresis ◽  
Platelet Membrane ◽  
Low Molecular Weight ◽  
Membrane Glycoproteins ◽  
Membrane Component ◽  
Before And After

SummaryAnalysis of platelet membrane proteins and glycoproteins by SDS Polyacrylamide gel electrophoresis was carried out before and after treatment with thrombin. Extended incubation with thrombin (in the presence of EDTA or adenosine, which inhibit aggregation) produced extensive changes in the bands observed. With incubation times of a few minutes however, the changes were restricted to a glycopeptide, GP IV (approx. 90,000 Daltons) and one or two polypeptides of low molecular weight, in particular polypeptide 16 (approx. 23,000 Daltons). At 0–3° C only polypeptide 16 was still hydrolyzed.Chymotrypsin, which does not activate platelets, attacked glycopeptides I, II, III but no changes were apparent in GP IV and polypeptide 16. When chymotrypsin-treated platelets were further incubated with thrombin, only GP IV and one to two low molecular weight polypeptides, especially polypeptide 16, were affected. As polypeptide 16 appears to be an integral membrane component it is possible that it, either by itself or in combination with GP IV, represents the primary thrombin substrate involved in platelet activation.Aggregated IgG, which also activates platelets, does not modify the membrane glycoproteins but does change the low molecular weight region in particular band 16.

Redistribution of Activation-Dependent Antigens on the Platelet Surface In Vivo and In Vitro.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3946-3946
Author(s):  
Yue Han ◽  
De Pei Wu ◽  
Lan Dai ◽  
Wenrong Sheng ◽  
Changgeng Ruan
Keyword(s):  
Cerebral Infarction ◽  
Platelet Activation ◽  
Normal Subjects ◽  
Platelet Membrane ◽  
Dependent Manner ◽  
Membrane Glycoproteins ◽  
Platelet Surface ◽  
Maximum Decrease

Abstract Platelets play a crucial role in thrombosis, platelet activation induces an alteration of platelet membrane glycoproteins between the platelet surface and surface connected canalicular system (SCCS). In an attempt to better understand this process and assess its significance in the study of thrombosis disease, we used flowcytometry for detecting the redistribution of antigens on the platelet surface following activation. The expression of platelet membrane glycoproteins (GP) Ib, IIIa and P-selectin as well as the platelet agglutination induced by ristocetin were measured in 20 normal subjects, whose platelets were stimulated by the peptide SFLLRNP(TRAP, thrombin receptor activated peptide) at different time points (0~30minute). The same antigens were also analyzed in whole blood in 30 patients with cerebral infarction. As expected, a stable increase of P-selectin was obtained from 2 minute upon TRAP activation, while a reversible reduction of GPIbα and agglutinability by ristocetin were showed at the same time, with a maximum decrease at 2 minute, then followed by a return of GP Ibα to platelet surface. In addition, the platelet membrane GPIIIa was not significantly changed in the initial stage after platelet stimulation and increased by degrees 10 minutes later. Compared with those in normal group, there was an apparent increase of P-selectin and a lower expression of GPIb in the patients with cerebral infarction, while GPIIIa was not significantly changed in all the samples. In summary, TRAP can mediate platelet activation, which leads to the redistribution of GPIb and GPIIIa in a time-dependent manner, together with the release of P-selectin. Meanwhile, the change of activation-dependent antigens on the platelet surface could be an important index reflecting the platelet activation in vivo.

Complex Formation Of Platelet Glycoproteins IIB And IIIA With Fibrinogen

1981 ◽  
Author(s):  
R Nachman ◽  
L Leung
Keyword(s):  
Complex Formation ◽  
Human Platelet ◽  
Platelet Membrane ◽  
Enzyme Linked Immunosorbent Assay ◽  
Macromolecular Complex ◽  
Two Dimensional ◽  
Membrane Glycoproteins ◽  
Human Fibrinogen ◽  
Platelet Surface ◽  
Lentil Lectin

Platelet membrane glycoproteins IIb and IIIa were isolated and purified from human platelet membranes using lentil lectin affinity chromatography and electrophoretic elution from SDS-poly-acrylamide gels. Two dimensional immunoelectrophoresis of a mixture of the purified proteins against monospecific antisera showed antigenic uniqueness of the separate polypeptides. Computerized analysis of autoradiographs of two dimensional tryptic 125I peptide maps revealed that the two glycoproteins had completely different structures. Thus human platelet membrane glycoproteins IIb and IIIa are separate molecular entities. Monospecific anti-GPIIb and anti-GPIIIa were utilized in an enzyme linked immunosorbent assay system to demonstrate complex formation of the platelet glycoproteins with purified human fibrinogen. The formation of this GPIIb-GPIIIa fibrinogen complex is calcium dependent, fibrinogen specific, saturable, and inhibited by specific amino sugars and amino acids. These observations suggest that the GPIIb-GPIIIa macromolecular complex on the platelet surface acts under the proper physiologic circumstances as the fibrinogen binding site required for normal platelet aggregation.

Rap1b Association with the Platelet Cytoskeleton Occurs in the Absence of Glycoproteins IIb/IIIa

1998 ◽  
Vol 79 (04) ◽  
pp. 832-836 ◽  
Author(s):  
Thomas Fischer ◽  
Christina Duffy ◽  
Gilbert White
Keyword(s):  
Molecular Weight ◽  
Divalent Cation ◽  
Binding Proteins ◽  
Binding Protein ◽  
Platelet Membrane ◽  
Low Molecular Weight ◽  
Membrane Glycoproteins ◽  
Gtp Binding Protein ◽  
Gtp Binding Proteins ◽  
Gtp Binding

SummaryPlatelet membrane glycoproteins (GP) IIb/IIIa and rap1b, a 21 kDa GTP binding protein, associate with the triton-insoluble, activation-dependent platelet cytoskeleton with similar rates and divalent cation requirement. To examine the possibility that GPIIb/IIIa was required for rap1b association with the cytoskeleton, experiments were performed to determine if the two proteins were linked under various conditions. Chromatography of lysates from resting platelets on Sephacryl S-300 showed that GPIIb/IIIa and rap1b were well separated and distinct proteins. Immunoprecipitation of GPIIb/IIIa from lysates of resting platelets did not produce rap1b or other low molecular weight GTP binding proteins and immunoprecipitation of rap1b from lysates of resting platelets did not produce GPIIb/IIIa. Finally, rap1b was associated with the activation-dependent cytoskeleton of platelets from a patient with Glanzmann’s thrombasthenia who lacks surface expressed glycoproteins IIb and IIIa. Based on these findings, we conclude that no association between GPIIb/IIIa and rap1b is found in resting platelets and that rap1b association with the activation-dependent cytoskeleton is at least partly independent of GPIIb/IIIa.

Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

1996 ◽  
Vol 16 (02) ◽  
pp. 114-138 ◽  
Author(s):  
R. E. Scharf
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Platelet Membrane ◽  
Clinical Aspects ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Membrane Expression ◽  
Receptor Complexes ◽  
Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

Human Blood Platelet Membrane Glycoproteins

1979 ◽  
Vol 42 (05) ◽  
pp. 1490-1502 ◽  
Author(s):  
C S P Jenkins ◽  
E F Ali-Briggs ◽  
G T E Zonneveld ◽  
A Sturk ◽  
J Clemetson
Keyword(s):  
Specific Problem ◽  
Sodium Dodecyl ◽  
Normal Subjects ◽  
Blood Platelet ◽  
Platelet Membrane ◽  
Buffer System ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Human Blood Platelet ◽  
Electrophoretic Techniques

SummaryThe separation of the major platelet membrane glycoproteins of normal subjects and subjects with well defined platelet membrane glycoprotein abnormalities have been examined using four different polyacrylamide gel electrophoretic techniques (continuous and discontinuous). The mobilities of the resolved glycoprotein bands have been correlated with the glycoprotein nomenclature proposed for the conventional sodium dodecyl sulphate- phosphate buffer system. Since the glycoprotein distribution varies depending on the system used, the merits of each method should be considered before application to a specific problem.

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